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Effect of a short-term diet and exercise intervention on oxidative stress, inflammation, MMP-9, and monocyte chemotactic activity in men with metabolic syndrome factors
Abstract
The present study was designed to examine the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation, chemotaxis, and cell adhesion. Obese men (n = 31), 15 of whom had metabolic syndrome, were placed on a high-fiber, low-fat diet in a 3-wk residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and postintervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin (for estimation of insulin sensitivity), oxidative stress-generating enzyme myeloperoxidase and marker 8-isoprostaglandin F2alpha, the inflammatory protein C-reactive protein, soluble ICAM-1 as an indicator of endothelial activation, sP-selectin as a marker of platelet activation, the chemokine macrophage inflammatory protein-1alpha, and total matrix metalloproteinase-9. Using subject sera and human aortic endothelial cell culture systems, we measured VCAM-1 cell surface abundance and monocyte chemotactic protein-1, nitric oxide, superoxide, and hydrogen peroxide production in vitro by fluorometric detection. Also determined in vitro was serum-induced, monocyte adhesion and monocyte chemotactic activity. After 3 wk, significant reductions (P < 0.05) in body mass index, all serum lipids and lipid ratios, fasting glucose, insulin, homeostasis model assessment for insulin resistance, myeloperoxidase, 8-isoprostaglandin F2alpha, C-reactive protein, soluble ICAM-1, soluble P-selectin, macrophage inflammatory protein-1alpha, and matrix metalloproteinase-9 were noted. In vitro, serum-stimulated cellular VCAM-1 expression, monocyte chemotactic protein-1 production, and fluorometric detection of superoxide and hydrogen peroxide production decreased, whereas a concomitant increase in NO production was noted (all P < 0.01). Additionally, both monocyte adhesion (P < 0.05) and MCA (P < 0.01) decreased. Nine of 15 were no longer positive for metabolic syndrome postintervention. Intensive lifestyle modification may ameliorate novel coronary artery disease risk factors in men with metabolic syndrome factors before reversal of obesity.
... Although increased low-density lipoprotein (LDL-c) and decreased highdensity lipoprotein (HDL-c) are considered to determine the risks of cardiovascular disease, reports show people who suffer from cardiovascular disease despite normal levels of LDL-c and HDL-C (1-3). Meanwhile, a lot of research suggests that cardiovascular disease has inflammatory background and that systemic inflammation plays a pivotal role in the development of atherosclerosis (4)(5)(6). Accordingly, in the past decade, more attention has been focused on inflammatory markers as independent factors that predict incidence of cardiovascular disease. Intercellular adhesion molecule-1 (ICAM-1) and C-reactive protein (CRP) act as important inflammatory markers, which are associated with the pathogenesis of atherosclerosis (4,(7)(8). ...
... This results in greater adherence of plaque and LDL particles to endothelial cells that finally leads to the development of a mature atherosclerotic plaque (4,15,16). Researchers have used different nutritional and exercise training approaches to reduce the activation of endothelial cells and subsequently inhibit the expression of adhesion molecules (6)(7)(8)(9)(17)(18)(19). In this regard, vitamin E supplementation has been suggested to decrease monocyte chemotactic activity (20) and surface expression of ICAM-1 induced by high-fat diet as it reduces the inflammatory marker (16). ...
... In this regard, vitamin E supplementation has been suggested to decrease monocyte chemotactic activity (20) and surface expression of ICAM-1 induced by high-fat diet as it reduces the inflammatory marker (16). Also, it has been shown that daily treadmill walking (70 to 85% of maximum heart rate) (6) and cycle ergometer training (80% of maximum heart rate) (7) with modified nutritional diet (high fiber, low fat) reduce ICAM-1 and CRP levels in diabetes mellitus type 2 and coronary artery disease, respectively (6,7). Furthermore, both short-(6, 15) and longterm (21) aerobic exercise training with moderate intensity alters circulating ICAM-1 and CRP in sedentary obese and overweight adults with metabolic syndrome. ...
... The effect of training on gelatinase plasma or serum concentrations was studied in old sedentary women, [38] in men with MS factors, [39] in subjects with asymptomatic coronary artery disease or cardiovascular risk factors [40] and in patients with type 2 diabetes mellitus. [41] In these studies training consisted in walking or running, except for elderly women, [38] who performed exercises aiming at increasing synchronization, dexterity, flexibility, strength, and steadiness. ...
... [ In a group of healthy postmenopausal women a walking program at 60% to 65% of the heart rate reserve 5 days per week for 8 weeks, failed to induce changes in MMP-9 and TIMP-1 levels, maybe because intensity and duration were too low. [42] In the studies described so far the decrease in MMP-9 concentration was paralleled by a reduction of several inflammation markers, including C-reactive protein, [39][40][41] fibrinogen, [41] soluble intracellular adhesion molecule-1, soluble Pselectin, and macrophage inflammatory protein-1a. [39] MMP-9 decreased also when body weight did not change significantly during the study. ...
... [42] In the studies described so far the decrease in MMP-9 concentration was paralleled by a reduction of several inflammation markers, including C-reactive protein, [39][40][41] fibrinogen, [41] soluble intracellular adhesion molecule-1, soluble Pselectin, and macrophage inflammatory protein-1a. [39] MMP-9 decreased also when body weight did not change significantly during the study. [41] A study by Lucotti et al [43] compared 2 types of 3-week training, including respectively only aerobic exercise or aerobic exercise with a supplement of resistance exercises, in obese type 2 diabetic patients. ...
Background
Matrix metalloproteinases (MMPs), particularly gelatinase A (MMP-2) and gelatinase B (MMP-9), as well as their tissue inhibitors (TIMP-1 and TIMP-2), are involved in the development of skeletal muscle tissue, in the repair process after muscle injury and in the adaptive modifications induced by physical exercise in skeletal muscle. This paper aims at reviewing results from human studies that investigated the role of gelatinases and their inhibitors in skeletal muscle response to acute physical exercise or training.
Methods
Electronic databases PubMed/MEDLINE, Scopus and Web of Science were searched for papers published between January 2000 and February 2017. The papers were eligible when reporting human studies in which MMP-2 and/or MMP-9 and/or the inhibitors TIMP-1/TIMP-2 were evaluated, in blood or muscular tissue, before and after acute physical exercise or before and after a period of structured physical training. We included studies on healthy subjects and patients with chronic metabolic diseases (obesity, diabetes mellitus, metabolic syndrome—MS) or asymptomatic coronary artery disease. We excluded studies on patients with neurological, rheumatologic or neoplastic diseases.
Results
Studies conducted on muscle biopsies showed an early stimulation of MMP-9 gene transcription as a result of acute exercise, whereas MMP-2 and TIMP transcription resulted from regular repetition of exercise over time. Studies on serum or plasma level of gelatinases and their inhibitors showed an early release of MMP-9 after acute exercise of sufficient intensity, while data on MMP-2 and TIMP were more contrasting. Most of the studies dealing with the effect of training indicated a trend toward reduction in blood gelatinase levels, once again more clear for MMP-9. This result was related to an anti-inflammatory effect of regular exercise and was more evident when training consisted of aerobic activities. This study has limitations: as the initial selection was done through titles and abstracts, incomplete retrieval cannot be excluded, as well as we cannot exclude bias due to selective reporting within studies.
Conclusion
A better knowledge of the molecular events activated by different types of acute exercise and regular training could be of great relevance in order to maximize the benefits of physical activity in healthy subjects and patients.
... Taken together, data from these studies indicate that exercise training reduces the circulating levels of CRP. Several prospective studies examining the influence of exercise training alone or incorporated in multi-disciplinary cardiac rehabilitation programs (exercise training program, dietary and lifestyle counseling, psychological support) on markers of inflammation, have suggested an anti-inflammatory effect of chronic exercise (6,14,16,33,46,52,53,(60)(61)(62)(63)67,68,71,73,76,77,80,84,86,87,90,(92)(93)(94)101,103,105,(107)(108)(109)117,121,125) (Table 1). As pointed out in Table 1, the majority of evidence suggests that exercise training is related to improvement in low-grade inflammatory markers as expressed by circulating CRP levels. ...
... Therefore, these molecules are considered to be important markers of endothelial cell activation and inflammation (35). Several studies explored the effect of exercise training on adhesion molecules (1,62,71,86,93,98,101,105). Exercise training exerts a positive impact on circulating cellular adhesion molecules ( Table 2). ...
... In healthy adults, acute ingestion of 19 saturated fat reduced HDL ability to inhibit the expression of markers of vascular inflammation in 20 endothelial cells [19]. In overweight/obese patients, a short-term low-fat diet restored the anti-21 inflammatory properties of dysfunctional HDL [20,21] and decreased HDL oxidized substrates and 22 oxidation potential [22]. However, in these studies the cholesterol content of the diet was not 23 quantified. ...
... However, in these studies the cholesterol content of the diet was not 23 quantified. Furthermore, the low-fat diet was coupled with either daily aerobic exercise [20,21] or 24 caloric restriction [22] and led to a significant loss of body weight, which is a major determinant of 25 M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 4 HDL concentration and function [1]. Thus, the specific effects of dietary cholesterol and fat on HDL 26 composition and function could not be determined. ...
Background and Aims
High-cholesterol and high-fat diets alter biochemical composition and anti-oxidant properties of high-density lipoproteins (HDL) in animals. Whether this occurs in humans is unknown. Therefore, we examined the effect of a short-term elevation in dietary cholesterol and fat intake on HDL composition in healthy subjects.
Methods and Results
In a randomized, crossover clinical trial, 14 healthy young volunteers followed a 14-day low-cholesterol/low-fat diet (LChF) and a 14-day isocaloric high-cholesterol/high-fat diet (HChF) in a random order. After each diet, we measured HDL concentrations of hydroxyeicosatetraenoic acids (HETE), hydroxyoctadecadienoic acids (HODE), and haptoglobin, as well as serum amyloid A (SAA) and paroxonase-1 activity (PON-1). HDL concentrations of 15-HETE (+254%, p=0.002), 5-HETE (+116%, p=0.004), 13-HODE (+102%, p=0.049), and SAA levels (+75%, p=0.007) were significantly higher after the HChF than after the LChF. Furthermore, haptoglobin was marginally increased (+32%, p=0.091) while PON-1 activity was unaffected (-16%, p=0.366) by the HChF.
Conclusion
In healthy subjects, a short-term elevation in dietary cholesterol and fat intake increased HDL lipid hydroperoxide content (15-HETE, 5-HETE, 13-HODE) and SAA levels, which are key features of dysfunctional HDL. This is the first study showing that a physiologic manipulation of dietary cholesterol and fat intake affects HDL lipidome and proteome in healthy subjects independently of weight changes.
Clinical Trial Registration
NCT02549144.
... We identified 15 studies investigating the effect of weight loss interventions (diet-and/ or exercise-, and surgery-induced) on individuals' oxidative stress level ( table 1 ): 6 RCTs and 9 non-randomized intervention studies (n = 5 diet, n = 6 diet and/or exercise interventions, and n = 3 bariatric surgery interventions) [35][36][37][38][39][40][41][42][43][44][45][46][47][48] . All studies measured oxidative stress markers in blood samples (plasma or serum, e.g., enzyme activities, 8-isoprostane, 8-oxo-dG; for details see table 1 ) [35][36][37][38][39][40][41][42][43][44][45][46][47][48] . ...
... We identified 15 studies investigating the effect of weight loss interventions (diet-and/ or exercise-, and surgery-induced) on individuals' oxidative stress level ( table 1 ): 6 RCTs and 9 non-randomized intervention studies (n = 5 diet, n = 6 diet and/or exercise interventions, and n = 3 bariatric surgery interventions) [35][36][37][38][39][40][41][42][43][44][45][46][47][48] . All studies measured oxidative stress markers in blood samples (plasma or serum, e.g., enzyme activities, 8-isoprostane, 8-oxo-dG; for details see table 1 ) [35][36][37][38][39][40][41][42][43][44][45][46][47][48] . ...
Background:
Altered levels of markers of oxidative stress, DNA repair, and telomere integrity have been detected in obese individuals and may underlie the pathogenesis of obesity-related diseases. However, whether or not such effects are reversed by intentional weight loss has not been systematically reviewed.
Methods:
A literature search in PubMed/Medline identified 2,388 articles of which 21 studies (randomized controlled trial (RCT) (n = 10) and non-randomized intervention studies (n = 11)) were classified as testing the effects of intentional weight loss on i) oxidative stress (n = 15), ii) DNA repair (n = 2), and iii) telomere length (n = 4).
Results:
Across a broad range of intervention designs, diet-, exercise-, surgery-, balloon-induced weight loss regimens decreased oxidative stress measures. Studies investigating DNA repair capacity or telomere length as endpoints after weight loss were less common in number and yielded null or inconsistent results, respectively.
Conclusion:
While this systematic review supports a role for intentional weight loss in reducing obesity-associated oxidative stress, it is not clear whether the effects are primary outcomes or secondary to improvement in obesity-associated insulin resistance and/or chronic inflammation. Although the lack of effect of intentional weight loss on DNA repair capacity might be anticipated given that oxidative stress is reduced, additional studies are needed. The inconsistent effects of weight loss on telomere length or DNA repair suggest the need for a re-assessment of intervention designs and assay methodology to definitively address this topic.
... However, due to challenges faced by the pharmacologic therapies and surgery especially, in developing countries where poverty and access to quality healthcare are problems; it becomes clear that change of lifestyle such as dietary modification could be a viable therapeutic approach in managing MS. Roberts et al. 26 and Akbaraly et al. 27 reported significant changes in metabolic risk factors in individuals with MS following short-term and long-term dietary modifications. A preliminary study in our laboratory 28 indicated a positive impact of short term dietary modification on indices of inflammation, oxidative stress as well as cardiovascular risks. ...
... Adoption of a healthier lifestyle has been identified as an important step in reducing the excess cardiovascular risk associated with MS 25 . The observed progressive reduction in all the anthropometric indices (body weight, BMI, WC,HC, waist-hip ratio, WHtR, % body fat) and blood pressure readings (SBP and DBP), and the concomitant rise in HDL-C concentration from baseline through 12-month HDL-C level corroborates the reports of Roberts et al. 26 and Akbaraly et al. 27 who observed significant beneficial changes in the cardio-metabolic risk factors in MS subjects following short-term and long-term dietary modification. Our observation probably indicates that diet modification results in less energy storage and increased utilization of stored energy thereby, improving the cardio-metabolic risk factors as observed. ...
Objective:
This study evaluated the effects of a 12-month dietary modification on indices of inflammation and pro-thrombosis in adults with metabolic syndrome (MS).
Materials and methods:
This longitudinal study involved 252 adults with MS recruited from the Bodija market, Ibadan and its environs. Participants were placed on 20%, 30% and 50% calories obtained from protein, total fat and carbohydrate respectively and were followed up monthly for 12 months. Anthropometry and blood pressure were measured using standard methods. Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), fibrinogen, plasminogen activator inhibitor-1 (PAI-1)], interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured using spectrophotometric methods and ELISA as appropriate. Data was analysed using ANCOVA, Student's t-test, Mann-Whitney U and Wilcoxon signed-rank tests. P-values less than 0.05 were considered significant.
Results:
After 6 months of dietary modification, there was a significant reduction in waist circumference (WC), while the levels of HDL-C, fibrinogen and PAI-1 were significantly increased when compared with the corresponding baseline values. However, WC and fibrinogen reduced significantly, while HDL-C and IL-10 significantly increased after 12 months of dietary modification as compared with the respective baseline values.
Conclusion:
Long-term regular dietary modification may be beneficial in ameliorating inflammation and pro-thrombosis in metabolic syndrome.
... There was also significant heterogeneity across the studies likely due to the differences in study design, baseline weight and BMI, study duration, health status of the participants and gender distributions. Further, studies with a short duration [26,43,58,61] are likely to have not occurred for long enough to notice a significant change in biomarker levels whereas studies with a very long duration [37,44,54] are likely to have experienced a greater change in results compared to studies of an average duration. The calculation of the standardised means of the changes in endothelial function biomarkers allowed the evaluation of the effect of weight loss on a combined estimate of different markers of endothelial function. ...
Endothelial dysfunction is closely linked to the development of atherosclerosis. This systematic review and meta-analysis reviewed the evidence on the effect of weight loss, achieved by dietary-based interventions, on biomarkers of endothelial function (EF). Two databases (Medline, Embase) were searched from inception until November 2022 for studies that met the following criteria: 1) adult subjects (≥ 18 years) without exclusion for health status, 2) dietary interventions for weight loss, and 3) measurements of changes in EF biomarkers. Random-effect meta-analysis and meta-regression were performed. Thirty-seven articles including 1449 participants were included in the systematic review. Study duration ranged from 3-52 weeks. Overall, weight loss significantly improved biomarkers of EF [standardised mean difference (SMD):0.65; 95%CI:0.49,0.81; P < 0.001;I2 = 91.9%]. Subgroup analyses showed weight loss significantly improved levels of E-selectin (P < 0.001), intercellular adhesion molecule-1 (ICAM-1) (P < 0.001), vascular cell adhesion molecule-1 (VCAM-1) (P < 0.001), nitrite/nitrate (NOx) (P < 0.001) and vascular endothelial growth factor (VEGF) (P < 0.001). Conversely, there was no significant improvement for von Willebrand Factor (vWF). Meta-regression analysis revealed that changes in EF biomarkers were not affected by age, BMI, quality of the studies or the amount of weight lost. A significant heterogeneity was observed for the effects of weight loss on changes in EF biomarkers. Dietary-induced weight loss may be associated with biomarkers changes indicating an improvement of EF, and it may represent a potential strategy to reduce atherosclerotic risk.
... To give strength to these data, a clinical study on patients with metabolic syndrome showed that when submitted to a regime with a high fiber/low-fat content and daily aerobic exercise for 3 weeks, their total level of serum MMP9 was significantly reduced along other markers of inflammation and oxidative stress as well as a significant decrease in circulating lipids, fasting blood glucose, insulin, and HOMA-IR index [45]. ...
Matrix metalloproteinases (MMPs) are a family of zinc-activated peptidases that can be classified into six major classes, including gelatinases, collagenases, stromelysins, matrilysins, membrane type metalloproteinases, and other unclassified MMPs. The activity of MMPs is regulated by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). MMPs are involved in a wide range of biological processes, both in normal physiological conditions and pathological states. While some of these functions occur during development, others occur in postnatal life. Although the roles of several MMPs have been extensively studied in cancer and inflammation, their function in metabolism and metabolic diseases have only recently begun to be uncovered, particularly over the last two decades. This review aims to summarize the current knowledge regarding the metabolic roles of metalloproteinases in physiology, with a strong emphasis on adipose tissue homeostasis, and to highlight the consequences of impaired or exacerbated MMP actions in the development of metabolic disorders such as obesity, fatty liver disease, and type 2 diabetes.
... As the only independent risk factor, MetS significantly influences long-term postoperative survival. Recent studies have demonstrated that short-term preoperative lifestyle interventions could effectively reduce or even reverse MetS (24). Therefore, future studies should focus on whether preoperative interventions can improve the prognosis of patients with CRC by reversing MetS. ...
Background
Metabolic syndrome (MetS) is associated with poor prognosis in many cancers. However, the relationship between metabolic syndrome and overall survival (OS) in patients with colorectal cancer (CRC) remains unclear. We aimed to comprehensively analyze whether MetS could affect postoperative complications and long-term survival in patients with CRC.
Methods
We included patients who underwent CRC resection at our center between January 2016 and December 2018. Bias was reduced through propensity score matching analysis. Patients with CRC were divided into the MetS and non-MetS groups based on whether they had MetS. Univariate and multivariate analyses were used to identify risk factors affecting OS.
Results
We included 268 patients; among them, 120 were included for further analysis after propensity score matching. There were no significant between-group differences in the clinicopathological features after matching. Compared with the non-MetS group, the MetS group had a shorter OS (P = 0.027); however, there was no significant between-group difference in postoperative complications. Multivariate analysis revealed that MetS (hazard ratio [HR] = 1.997, P = 0.042), tumor-node-metastasis stage (HR = 2.422, P = 0.003), and intestinal obstruction (HR = 2.761, P = 0.010) were independent risk factors for OS.
Conclusions
MetS affects the long-term survival of patients with CRC without affecting postoperative complications.
... In addition, insulin sensitivity and EC function in insulin-resistant individuals can be improved by reducing body weight through PA [40]. It also reduces inflammatory cytokine levels through improvement of EC function [41], and PA make a positive impact on EC function by increasing the bioavailability of nitric oxide [42]. ...
Background
Previous studies have suggested that blood Cd, Pb exposure, and physical activity levels may influence the development of hypertension. This study aimed to investigate the relationship between blood Cd, Pb levels, and hypertension by the level of physical activity in Korean adults using The Korea National Health and Nutrition Examination Survey (KNHANES).
Methods
We used data from the KNHANES (2008–2013), a nationally representative, cross-sectional, population-based study. We included 8,510 participants who had records of blood Cd, Pb and, blood pressure measurements. Multiple logistic regression was used to examine the association between blood Cd and Pb exposure and the development of hypertension, as well as the modifying effects of physical activity levels. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S).
Results
Following covariates adjustments, we found significant associations of blood Cd and Pb with higher hypertension prevalence. This association was more apparent in low physical activity while blood Cd and Pb concentrations were not significantly associated with hypertension in participants with more activity. Additionally, there was a significant interaction between blood Cd and physical activity on hypertension risk (RERI = 0.17, 95% CI: -0.36–0.7; AP = 0.12, 95% CI: -0.28–0.52; S = 1.75, 95% CI:1.36–2.14).
Conclusions
Our results suggest that low physical activity may substantially amplify the adverse effects of blood Pb and Cd exposure on hypertension risk. However, interactions were only found for Cd. Further studies are needed to confirm these findings.
... Снижаются адгезия моноцитов и их хемотаксическая активность. Отмечается, что у 9 из 15 участников по результатам применения соответствующей диеты был отменен диагноз метаболического синдрома [6]. В Китае, Японии и Корее в качестве популярного лекарственного средства используют гриб Phellinus linteus, полученные из него экстракты проявляют антиканцерогенную, противовоспалительную и антиоксидантную активность, способны снижать содержание медиаторов воспаления, таких как оксид азота, фактор некроза опухоли альфа (TNF-α), интерлейкин-6 и моноцитарный хемотаксический фактор 1 (MCP-1), индуцированные либо липополисахаридами (ЛПС), либо кондиционированной средой, полученной из адипоцитов и в кокультурах адипоцитов и макрофагов. ...
The literature review presents the results of modern studies of the relationship between diet and intestinal microbiota in the regulation of metabolic disorders. Metabolic syndrome, which is a symptom complex that combines abdominal obesity, insulin resistance, hyperglycemia, dyslipidemia and arterial hypertension, remains an important problem, being a risk factor for cardiovascular, neurodegenerative, oncological diseases and the development of type 2 diabetes mellitus. Although the pathogenesis of the metabolic syndrome has not yet been fully elucidated, it is known that visceral obesity and its associated complications, such as dyslipidemia and increased levels of pro-inflammatory cytokines, play a central role. The article presents data on the impact of the consumption of certain food products, the inclusion of plant biologically active substances (flavonoids, polyphenols, etc.) in the diet, as well as the use of elimination diets with the exclusion of carbohydrates or fats from the diet, on reducing the risk of cardiovascular accidents, levels of fasting glucose, total cholesterol, LDL, triglycerides, C-reactive protein, leptin, insulin, reduction in body weight and waist circumference, reduction in the level of circulating endotoxins and changes in the activity of immunocompetent cells. Data are presented on the possible influence of the intestinal microbiota in maintaining inflammation and the formation of degenerative changes in the body. The role of changes in the ratio of the levels of pathogenic microflora, bifidobacteria and lactobacilli in the formation of a pathological condition is shown.
... Previous research reports suggested a 43% decrease in overall mortality in BC survivors who consumed high-vegetable and -whole grain diets (267). Another study indicated a decrease in serum CRP, matrix metalloproteinase 9 (MMP-9), vascular cell adhesion molecule 1 (VCAM), and Pselectin levels in patients on a high-fiber and low-fat diet (268). A low-fat diet reduced the risk of invasive BC, suggesting that a low fat intake has potential long-term benefits (269). ...
Obesity and associated chronic inflammation were shown to facilitate breast cancer (BC) growth and metastasis. Leptin, adiponectin, estrogen, and several pro-inflammatory cytokines are involved in the development of obesity-driven BC through the activation of multiple oncogenic and pro-inflammatory pathways. The aim of this study was to assess the reported mechanisms of obesity-induced breast carcinogenesis and effectiveness of conventional and complementary BC therapies. We screened published original articles, reviews, and meta-analyses that addressed the involvement of obesity-related signaling mechanisms in BC development, BC treatment/prevention approaches, and posttreatment complications. PubMed, Medline, eMedicine, National Library of Medicine (NLM), and ReleMed databases were used to retrieve relevant studies using a set of keywords, including “obesity,” “oncogenic signaling pathways,” “inflammation,” “surgery,” “radiotherapy,” “conventional therapies,” and “diet.” Multiple studies indicated that effective BC treatment requires the involvement of diet- and exercise-based approaches in obese postmenopausal women. Furthermore, active lifestyle and diet-related interventions improved the patients’ overall quality of life and minimized adverse side effects after traditional BC treatment, including postsurgical lymphedema, post-chemo nausea, vomiting, and fatigue. Further investigation of beneficial effects of diet and physical activity may help improve obesity-linked cancer therapies.
... 89 No such agent is available that can offer a synergistic approach in treating the different phenotypes of TLD by targeting OS. Lifestyle modification, 90 correcting metabolic syndrome, 91,92 exercise, diet, weight loss, 93,94 and the use of antioxidants can target OS. Early intervention with antioxidant therapy can prevent or improve TLD. ...
Chronic liver disease (CLD) is a leading health problem impacting the quality of life globally. China shares major global burden of CLD—including alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI), except for chronic viral hepatitis. Several exogenous toxins or endogenous metabolic insults trigger hepatic pathology toward steatosis, inflammation, and fibrosis, which, if left untreated, may culminate in liver cirrhosis. Oxidative stress (OS) is a common pathomechanism underlying all phenotypes of toxic liver injury; thus, these may be brought under a unified entity, viz. toxic liver disease (TLD). Therefore, a common strategy to treat TLD is to use antioxidants as hepatoprotective agents. The cornerstone for treating fatty liver disease (FLD) is lifestyle modification, diet, exercise, and behavioral therapy, along with limited use of pharmacological agents. Available preclinical and clinical evidence indicates that silymarin is a hepatoprotective agent with established antioxidant, anti-inflammatory, anti-fibrotic effects. An international expert panel of clinicians was convened to discuss combining ALD, NAFLD/MAFLD, DILI, and liver cirrhosis under the single definition of TLD, based on the shared pathological mechanism of oxidative stress. The panel highlighted the significance of silymarin as an antioxidant treatment for TLD.
... The increased HDL-C in the present study is consistent with Roberts et al. [34] who demonstrated improvements in HDL-C function after only 3 weeks of training and dietary intervention in patients at risk for metabolic syndrome. In addition, Tjønna et al. [26] reported significant improvements in HDL-C concentration along with improvements in body composition in the HIIT group after 3 months of training. ...
Background
Menopause is associated with changes in body composition and distribution, as well as reduced estradiol level that affect the development and progression of fatty liver diseases.
Aims
To determine anthropometric measurements, lipid and estradiol levels, and size of liver in response to diet and high-intensity interval training (HIIT) in postmenopausal women with hepatic steatosis.
Setting and design
A single blind, randomized controlled trial was conducted on a total of 56 postmenopausal women with hepatic steatosis.
Patients and methods
Participants were randomized to one of two groups. Diet group consisting of 30 patients received hypocaloric diet for 12 weeks, while diet–HIIT group consisting of 26 patients received hypocaloric diet and HIIT three times/week for 12 weeks. Anthropometric measurements including weight, BMI, and waist girth were taken. Blood samples were collected to determine the levels of lipids, including total cholesterol, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol, as well as estradiol level. Also, ultrasonography was used to measure the liver size. All outcomes were measured at starting and after 12 weeks of the treatment course.
Results
The diet–HIIT group showed a greater decrease in the waist girth (0.0001), TG (P=0.002), and liver size (P=0.005), as well as a greater increase in HDL-C (P=0.03) and estradiol level (P<0.0001) than the diet group. Linear regression analysis showed that the mean change in estradiol level accounted for 52% of variability in the liver size.
Conclusion
Hypocaloric diet–HIIT intervention is a more effective treatment for improving waist girth, HDL-C, TGs, estradiol level, and liver size than hypocaloric diet alone. The mean change of estradiol level is a significant predictor for improving liver size in obese postmenopausal women with hepatic steatosis.
... The present study confirms such findings in statin-free diabetic patients after a moderately intense exercise programme. Similarly, two other studies have shown significant downregulation of MMP-9 levels after a combined diet and exercise intervention in children and in men with metabolic syndrome risk factors [32,33]. Although it is difficult to distinguish the sole effects of exercise in these two studies, both underscored the beneficial influence of lifestyle modification on MMP-9 levels. ...
Aim
To evaluate the effects of exercise training (ET) on cardiac extracellular matrix (ECM) proteins homeostasis and cardiac dysfunction in mice with diabetic cardiomyopathy.
Methods
Thirty-six male C57BL/6 mice were randomized into 3 groups for 8 weeks (12mice/group): Diabetic control-DC: Diabetes was induced by single streptozotocin injection (200mg/kg i.p.); Diabetic exercise-DE: Diabetic mice underwent ET program on motorized-treadmill (6-times/week, 60min/session); Non-diabetic control-NDC: Vehicle-treated, sedentary, non-diabetic mice served as controls. Before euthanasia, all groups underwent transthoracic echocardiography (TTE). Post-mortem, left-ventricle (LV) samples were histologically analysed for ECM proteins (collagen, elastin), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs).
Results
DC group showed significantly higher cardiac contents of collagen and MMP-9 and lower elastic concentration than NDC (p < 0.001). The implementation of ET completely outweighed those diabetes-induced changes (DE vs NDC, p > 0.05). TIMP-1 levels significantly increased across all groups (DC: 18.98 ± 3.47%, DE: 24.24 ± 2.36%, NDC: 46.36 ± 5.91%; p < 0.05), while MMP-9/TIMP-1 ratio followed a reverse pattern. ET tended to increase MMP-2 concentrations versus DC (p = 0.055), but did not achieve non-diabetic levels (p < 0.05). TIMP-2 cardiac concentrations remained unaltered throughout the study (p > 0.05). Importantly, ET ameliorated both LV end-systolic internal diameter (LVESD) (p < 0.001) and the percentage of LV fractional shortening (FS%) (p = 0.006) compared to DC. Despite that favorable effect, the cardiac function level of DE group remained worse than NDC group (%FS: p = 0.002; LVESD: p < 0.001).
Conclusion
Systemic ET may favorably change ECM proteins, MMP-9 and TIMP-1 cardiac concentrations in mice with diabetic cardiomyopathy. Those results were associated with partial improvement of echocardiography-assessed cardiac function, indicating a therapeutic effect of ET in diabetic cardiomyopathy.
... This effect, however, can vary depending on the type, intensity and duration of the interventions. As shown by Roberts et al. (2006) the combination of daily aerobic exercise and a low-fat, high fiber diet in healthy patients and patients with metabolic syndrome induced a reduction of inflammation, leucocytes adhesion and chemotaxis capacity, and oxygen species production as well as a decrease in metabolic syndrome markers after 3 weeks of treatment. Moreover, the experiments by Hill et al. (2007) suggested combining diet and exercising interventions to enforce the immunity and to prevent obesity, cardiovascular diseases and diabetes mellitus. ...
Physical activity (PA) and nutrition are the essential components of a healthy lifestyle, as they can influence energy balance, promote functional ability of various systems and improve immunity. Infections and their associated symptoms are the common and frequent challenges to human health that are causing severe economic and social consequences around the world. During aging, human immune system undergoes dramatic aging-related changes/dysfunctions known as immunosenescence. Clinically, immunosenescence refers to the gradual deterioration of immune system that increases exposure to infections, and reduces vaccine efficacy. Such phenomenon is linked to impaired immune responses that lead to dysfunction of multiple organs, while lack of physical activity, progressive loss of muscle mass, and concomitant decline in muscle strength facilitate immunosenescence and inflammation. In the present review, we have discussed the role of nutrition and PA, which can boost the immune system alone and synergistically. Evidence suggests that long-term PA is beneficial in improving immune system and preventing various infections. We have further discussed several nutritional strategies for improving the immune system. Unfortunately, the available evidence shows conflicting results. In terms of interaction with food intake, PA does not tend to increase energy intake during a short time course. However, overcoming nutritional deficiencies appears to be the most practical recommendation. Through the balanced nutritious diet intake one can fulfill the bodily requirement of optimal nutrition that significantly impacts the immune system. Supplementation of a single nutrient as food is generally not advisable. Rather incorporating various fruits and vegetables, whole grains, proteins and probiotics may ensure adequate nutrient intake. Therefore, multi-nutrient supplements may benefit people having deficiency in spite of sufficient diet. Along with PA, supplementation of probiotics, bovine colostrum, plant-derived products and functional foods may provide additional benefits in improving the immune system.
... Mediterranean diet is a rich in plant-based foods (cereals, fruits, vegetables, legumes, nuts, oilseeds); the main oil source is olive oil; fish and seafood consumption is high; eggs, poultry and dairy products consumption is moderate; red meat and processed meat consumption is low (Bach-Faig et al., 2011;Pekcan, 2019). Adherence to the Mediterranean diet has been shown to reduce the level of inflammatory factors (C-reactive protein, IL-6) in serum even in a very short period of time (Hadziabdic et al., 2012;Roberts et al., 2006). The Mediterranean diet is included in the nutrition policies of many countries, including our country, as a health-protective diet recommendation (TÜBER, 2016). ...
Noncommunicable diseases (cardiovascular diseases, cancer, chronic respiratory diseases and diabetes etc.), also known as chronic diseases, are the leading causes of global deaths. Oxidative stress and inflammation are important underlying factors in the development of these diseases and are directly related to nutrition. The oxidative and inflammatory response due to nutrition may occur in the long term, as well as immediately following meal consumption. It is known that each meal produces a short-term and a certain level of oxidative and inflammatory responses in the postprandial state depending on the energy content and pattern. Nutritional factors that cause postprandial oxidative stress and inflammatory response are energy, carbohydrate and fat contents of the meal. It is known that frequent recurrence of acute responses that start in the postprandial state and its chronic exposure may play an important role in the development of chronic diseases such as cancer, diabetes and cardiovascular diseases in the long term. Considering that nowadays most of the days are spent in the postprandial state, the importance of the energy content and pattern of the meals has increased. In this review, the effects of meal consumption and nutrition on postprandial oxidative stress and inflammation metabolism were investigated. GUHES 2-2 (2020) 800038
... tools that can be used to characterize these subtle deficits in vulnerable populations before clinically meaningful decline. Targeting those at risk in this early stage may increase the efficacy of minimally invasive lifestyle-based interventions effective in managing inflammation, such as diet and exercise (Carvalho-Wells et al., 2012;Llorente-Cortés et al., 2010;Milani et al., 2004;Roberts et al., 2006;Stewart et al., 2007). This is particularly important when considering the young age of the current sample, and the potential for further decline without proper management of systematic inflammation. ...
Elevated serum C-reactive protein (CRP) and possessing an APOE ε4 allele are two of the most prominent risk factors for cognitive and neurological dysfunction in older adults, but little is known about the unique or cumulative effects of these risk factors in young-to-middle aged adults. To further characterize these potential relationships, measures of cognition and microstructural white matter integrity were examined using data from a sample of 329 post-9/11 war veterans that was collected as part of a comprehensive evaluation that included assessment of neuropsychological functioning, MRI scanning, psychiatric diagnoses, health screening, markers of inflammation, and APOE genotypes. Hierarchical linear regression analyses revealed the CRP and APOE ε4 interaction was associated with global cognition (β = -.633), executive functioning (β = -.566), and global fractional anisotropy (β = -.470); such that elevated CRP was associated with worse cognition and white matter integrity in APOE ε4 carriers. Diffusion tensor imaging (DTI) was used to determine if CRP x APOE ε4 presence was associated with regionally specific fractional anisotropy in white matter tracts. Tract-Based Spatial Statistics revealed CRP x APOE ε4 presence was associated with fractional anisotropy in the corpus callosum, right superior longitudinal fasciculus, right posterior corona radiata, as well as the bilateral anterior and superior corona radiatas. This suggests that APOE ε4 carriers may be uniquely vulnerable to the potentially negative impact of elevated systematic inflammation to cognition and microstructural white matter integrity.
... The above results indicate that the effect of training is observable when it accompanies a diet. Some researchers emphasized the simultaneous adjustment of daily physical activity and diet as one part of correcting lifestyle in order to improve lipid and inflammatory profile and showed that due to the positive relationship between the level of plasma inflammatory indicators with blood lipids and some anthropometric factors like BMI, fat percentage and waist to hip, a low-fat and high-fiber diet and exercise are necessary in this regard [33]. Physical activity may adjust the effective mechanisms in regulating adhesion molecules like renin angiotensin system and reducing the release of chemical mediators and inflammatory factors like NFK-B in adjusting the vascular inflammation. ...
Background: Drug consumption and addiction lead to serious cardiovascular diseases as well as inflammation. Cellular adhesion molecules are glycoproteins that mediate a leukocyte reaction to inflammation. This study aims to determine the effect of aerobic exercises on some cardiovascular factors in addicts treated with methadone. Methods: This is a semi-experimental research. To conduct this research, 30 male addicted patients treated with methadone with a mean age of 33.53±15.42 years, 70.06±15.42kg weight and 174.8±5.69cm were selected after medical screening and randomly divided into experimental (n=16) and control (n=16) groups. First, the height, weight and body mass index (BMI) of participants in both groups were measured. Blood samples were taken from the subjects in order to measure the intercellular adhesion molecules 1 (sICAM) and cellular vascular adhesion 1 (sVCAM) in serum. The experimental group had an aerobic exercise program including use of a treadmill with a 40 to 50% maximum heart rate in the beginning and then, a 70 to 80% maximum heart rate. The control group had only a follow-up. After 8 weeks, all variables were measured in both groups. Correlated t-test and independent t-test were used for intragroup and intergroup comparisons (P<0.05). Results: Results showed that after 8 weeks aerobic exercises, there was no significant difference in ICAM-1 (P=0.397), VCAM-1 (P=0.521), and BMI (P=0.223). Conclusion: Although 8-weeks aerobic exercise was not effective and sufficient for BMI, ICAM-1 and VCAM-1 indicators of the addicts treated with methadone, but it reduced ICAM-1 and VCAM-1 in the exercise group.
... Moreover, plasma malondialdehyde (MDA) concentrations spectrophotometrically were assayed by measurement of thiobarbituric acid reactive substances (TBARS) assay according to the procedure of Uchiyama and Mihara (1978) [22]. Serum 8-iso-PG F2α levels were measured in duplicate using an enzyme immunoassay kit (Cayman Chemicals Co., Ann Arbor, Michigan, USA) [23]. Moreover, the activity of superoxide dismutase (SOD) was measured at 500 nm with a commercially available kit (Randox Laboratories, kit Ransod superoxide dismutase). ...
Background: Strenuous acute exercise induces oxidative stress in the active muscles and circulation, However, consumption of products rich in antioxidants may potentially ameliorate these effects.
Objective: The present investigation was conducted to determine the effect of Artichoke (Cynara scolymus L.) extract on oxidative stress and antioxidant defense after aerobic exercise in young athletes.
Method: Twenty two subjects received 2400 ml/kg/day Artichoke-leaf extract or placebo capsule for a period of 14 days. All subjects of both groups underwent in acute aerobic exercise before and after 14 days supplementation. Blood samples were collected at pre supplementation, pre exercise, post exercise and 24 hours after exercise. Malondiadehyde (MDA), plasma total antioxidant capacity (FRAP), superoxide dismutase (SOD), and 8-iso-prostaglandin-F2α (8-iso-PGF2α) were measured.
Results: The results showed that concentration of MDA and Serum 8-iso-PG F2α, SOD, and plasma total antioxidant significantly increased at immediately and 24 hrs after aerobic exercise (P0.05), but after 24-h of exercise, 8-iso-PG F2α concentration in the group supplement was significantly lower in comparison to placebo group (P=0.002).
Conclusion: The results of this study indicated that a single session of strenuous aerobic exercise induces oxidative stress production and increase of antioxidant indices in young athletes. However, further studies are necessary to clarify the exact antioxidant effects of Artichoke extract in athletes.
... Another study showed elevated MMP-9 level in patients with metabolic syndrome [33]. Furthermore, 3-week of lifestyle modification (high fiber, low-fat diet and exercise) led to significant reduction of MMP-9 levels in patients with metabolic syndrome [34]. ...
The purpose of the article: Brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) are involved in the processes of neurogenesis, synaptic plasticity, learning and memory. Growing number of studies shows a relationship between BDNF or MMP-9 and schizophrenia. Also, BDNF and MMP-9 levels may be affected by metabolic parameters, such as obesity or dyslipidemia. Our hypothesis is that alterations of BDNF or MMP-9 levels in schizophrenia might be secondary to metabolic abnormalities, often found among schizophrenia patients.
Materials and methods: We have compared BDNF and MMP-9 between patients with schizophrenia (n = 64, age 49 ± 8.2 y) and healthy controls (n = 32, age 51 ± 8.9 y) in the context of cardio-metabolic parameters. Serum levels of BDNF and MMP-9 were measured using ELISA test, body composition parameters were determined using bioelectric impedance analysis.
Results and conclusions: Our results showed significantly lowered serum BDNF concentration in the schizophrenia group (schizophrenia: 23.8 ± 7.83 ng/mL, control: 27.69 ± 8.11 ng/mL, p = 0.03). Serum MMP-9 concentration in schizophrenia group did not differ compared with the control group (schizophrenia: 456.8 ± 278.4 ng/mL, control: 341.5 ± 162.4 ng/mL, p = 0.07). After adjusting for age, all anthropometric parameters, body composition and laboratory tests BDNF were still significantly lower in the schizophrenia group. However, MMP-9 became significantly elevated in the schizophrenia group after adjusting for several anthropometric and body composition covariates. Our results confirmed reduced serum BDNF concentration in patients with schizophrenia. Also, this reduction seems to be independent of metabolic abnormalities. On the other hand, our hypothesis that MMP-9 level in schizophrenia is altered due to metabolic abnormalities might be true.
... Nearly all known pathophysiologic contributors to sickling and vaso-occlusion, most notably inflammation, oxidative stress, endothelial/vascular dysfunction, and cell adhesion, represent mechanisms known potentially to be ameliorated with exercise training. [53][54][55][56][57][58] In the general population, for example, the long-term cardiovascular benefits of regular exercise are in part attributed to the attenuation over time of the acute-phase inflammatory response to acute exercise. 59 We see signals in the literature that exercise training may in fact have disease-modifying effects in SCT and SCA. ...
Development of exercise guidelines for individuals with sickle cell trait (SCT) and sickle cell anemia (SCA) is hampered by the need to weigh the benefits against risks of exercise in these populations. In SCT, concern for exercise collapse associated with sickle cell trait has resulted in controversial screening of student athletes for SCT. In SCA, there exists unsubstantiated concerns that high-intensity exercise may result in pain and other complications. In both, finding the "right dose" of exercise remains a challenge for patients and their providers. Despite assumptions that factors predisposing to adverse events from high-intensity exercise overlap in SCT and SCA, the issues that frame our understanding of exercise-related harms in both are distinct. This review will compare issues that affect the risk-benefit balance of exercise in SCT and SCA through these key questions: (1) What is the evidence that high-intensity exercise is associated with harm? (2) What are the pathophysiologic mechanisms that could predispose to harm? (3) What are the preventive strategies that may reduce risk? and (4) Why do we need to consider the benefits of exercise in this debate? Addressing these knowledge gaps is essential for developing an evidence-based exercise prescription for these patient populations.
... These differences may be attributable to differences in study population and/ or mode or intensity of exercise. Several studies have also examined the effect of exercise on chemotactic properties of monocytes, with a diet + exercise intervention reducing monocyte adhesion and chemotactic activity in obese men [50] and a 3 week exercise intervention reducing monocyte adhesion in a similar study [51]. ...
Monocytes are cells of the innate immune system which perform important functions, including inflammatory cytokine production and phagocytosis, and participate in pathogen defense. In aging and disease, monocyte functions are dysregulated, and this dysregulation has been conclusively linked to the pathogenesis of a variety of age-related chronic diseases. In this review, we summarize the current literature supporting exercise training as a potential therapy for improving monocyte function, with particular attention to studies in the aging population. Substantial evidence suggests exercise is an effective therapy for modulating monocyte biology, although mechanisms by which this occurs are still not well understood.
... By comparison, for example, of 855 enrolled participants in the HERITAGE study, 8 652 had complete data; that is, the rate of missing data was 23.7%. Reports of other trials, many of them smaller, also report equivalent or higher rates of missing data [68][69][70] or fail to report them at all. 18,[71][72][73][74] These studies suggest that the rate of missing data in our trial was typical for exercise training trials. ...
Background
Consensus panels regularly recommend aerobic exercise for its health‐promoting properties, due in part to presumed anti‐inflammatory effects, but many studies show no such effect, possibly related to study differences in participants, interventions, inflammatory markers, and statistical approaches. This variability makes an unequivocal determination of the anti‐inflammatory effects of aerobic training elusive.
Methods and Results
We conducted a randomized controlled trial of 12 weeks of aerobic exercise training or a wait list control condition followed by 4 weeks of sedentary deconditioning on lipopolysaccharide (0, 0.1, and 1.0 ng/mL)‐inducible tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), and on toll‐like receptor 4 in 119 healthy, sedentary young adults. Aerobic capacity by cardiopulmonary exercise testing was measured at study entry (T1) and after training (T2) and deconditioning (T3). Despite a 15% increase in maximal oxygen consumption, there were no changes in inflammatory markers. Additional analyses revealed a differential longitudinal aerobic exercise training effect by lipopolysaccharide level in inducible TNF‐α (P=0.08) and IL‐6 (P=0.011), showing T1 to T2 increases rather than decreases in inducible (lipopolysaccharide 0.1, 1.0 versus 0.0 ng/mL) TNF‐α (51% increase, P=0.041) and IL‐6 (42% increase, P=0.11), and significant T2 to T3 decreases in inducible TNF‐α (54% decrease, P=0.007) and IL‐6 (55% decrease, P<0.001). There were no significant changes in either group at the 0.0 ng/mL lipopolysaccharide level for TNF‐α or IL‐6.
Conclusions
The failure to support the primary hypotheses and the unexpected post hoc findings of an exercise‐training–induced proinflammatory response raise questions about whether and under what conditions exercise training has anti‐inflammatory effects.
Clinical Trial Registration
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01335737.
... and activates cytokines and chemokines [19]. Roberts et al. found elevated levels of MMP-9 in men with metabolic syndrome and observed that they displayed significant reductions in BMI, insulin, HOMA-IR, and MMP-9 after diet and exercise intervention [30]. In the study of Yu et al., subjects which exhibited at least one of the features of metabolic syndrome (i.e., central obesity, low HDL cholesterol, hypertension, elevated fasting blood glucose, and high TG) had also higher serum MMP-9 comparing to subjects without features of metabolic syndrome [31]. ...
Insulin resistance increases the risk for cardiovascular disease (CVD) even in the absence of classic risk factors, such as hyperglycemia, hypertension, dyslipidemia, and obesity. Low-grade chronic inflammatory state is associated both with insulin resistance and atherosclerosis. An increased circulating level of proinflammatory proatherogenic factors and biomarkers of endothelial activation was observed in diabetes and CVD. The aim of our study was to assess serum proatherogenic and proinflammatory factors in young healthy nonobese subjects with positive family history of type 2 diabetes. We studied 74 young healthy nonobese subjects with normal glucose tolerance (age < 35 years, BMI < 30 kg/m ² ), 29 with positive family history of type 2 diabetes (relatives, 25 males and 4 females) and 45 subjects without family history of diabetes (control group, 39 males and 6 females). Hyperinsulinemic-euglycemic clamp was performed, and serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin 18 (IL-18), macrophage inhibitory cytokine 1 (MIC-1), macrophage migration inhibitory factor (MIF), matrix metalloproteinase (MMP-9), and soluble forms of adhesion molecules were measured. Relatives had markedly lower insulin sensitivity ( p=0.019 ) and higher serum MMP-9 ( p<0.001 ) and MIF ( p=0.006 ), but not other chemokines and biomarkers of endothelial function. Insulin sensitivity correlated negatively with serum MMP-9 ( r=−0.23 , p=0.045 ). Our data show that young healthy subjects with positive family history of type 2 diabetes already demonstrate an increase in some nonclassical cardiovascular risk factors.
... Besides environmental factors including smoking, physical inactivity and atherogenic diet, genetic factors contribute in MS pathogenecity [14]. Many Genome Wide Association Studies (GWAS) were interested to test associations between genetic variants and disease trait. ...
... A atividade física regular reduz os riscos de morbidades relacionadas ao sedentarismo. Roberts e colaboradores concluíram que exercício aeróbico moderado, em conjunto com mudança nutricional, apresenta os seguintes resultados: 1) melhora nos perfis lipídicos e metabólicos, 2) redução no estresse oxidativo e aumento no óxido nítrico, 3) diminuição na inflamação sistêmica crônica, 4) redução na ativação de plaquetas e células endoteliais, 5) redução na adesão de monócitos e na sua atividade químico atrativa e 6) diminuição de metaloproteinase 9 (MMP-9), um biomarcador de desestabilização plaquetária 1 . ...
In order to contribute to lower prevalence of obesity and sedentarism rates, which are risk factors for various cardiometabolic diseases, the study elucidates the effects of different prescription models of exercise intensity concerning to psychophysiological markers and stress. The clinical trial consisted of a 60 minute treadmill exercise session with obese, sedentary, and healthy women (N = 46), aged 18-45 years, randomized into two groups (GAuto and GImp). Then, it was collected the affect scale, a momentary intensity of activity and plasma cortisol pre- and post-exercise. Thus, it was concluded that a moderate exercise in self-selected intensity is related to a higher intensity, better affective responses and a similar stress reduction, when compared to the imposed intensity exercise, which directly influences the adherence to an activity when it comes to overweight women.
... The effects of exercise on inflammatory biomarkers in CKD patients have been evaluated in some RCT, most of them in HD patients, in general with positive results [6]. Six studies in earlier stages of CKD assessed hs-CRP [23,[25][26][27][28][29], of which only one, that have also applied resistance training, found a positive association between exercise and reduction in this biomarker [25]. Considering that chronic inflammation is always present in CKD and may be a mediator of malnutrition, cardiovascular disease, progression to ESRD and poorer survival [30], the potential control of the inflammatory status through exercise, especially resistance training, is a noteworthy finding. ...
Hypertension and chronic kidney disease (CKD) are global public health problems, both associated with higher risk of cardiovascular (CV) and renal events. This trial randomized non-diabetic adult patients with hypertension and CKD stages 2–4 to 16 weeks of aerobic and resistance training or usual care. The primary outcome was the change in estimated glomerular filtration rate (eGFR). Secondary outcomes included changes in systolic and diastolic blood pressure (BP), body weight, fasting blood glucose, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and functional capacity. The analysis was performed by intention-to-treat, using linear mixed-effects models for repeated measures over time. A hundred fifty patients were included in the intervention (76) or control (74) groups. No difference was found in eGFR, BP, body weight, or lipid profile changes between the groups. However, there were significant decreases in hs-CRP [−6.7(−11.7 to −1.8) mg/L] and fasting blood glucose [−11.3(−20.0 to −1.8) mg/dL], and an increase in functional capacity [2′ Step Test 33.9 (17.7–50.0); 30″ Stand Test 2.3 (0.9–3.7)] in exercise group compared with control group. The results of this RCT show that combined aerobic and resistance training could reduce inflammation and insulin resistance in hypertensive patients with earlier stages of CKD, without a significant effect on kidney disease progression. Clinical trials.gov NCT01155128.
... Physical activity and VO 2 have been identified as perhaps the most important factors governing chronic disease risk, particularly CVD and DM [503]. Up to 50% of coronary artery disease can be prevented by 30 min of moderate exercise daily (assessed in middle-aged women) [504][505][506], and as little as 3 weeks of exercise can reduce the clinical impact of metabolic syndrome (a combination of coronary heart disease, hypertension and T2DM) by 50% [507]. Not only substantially reducing risk/incidence, exercise can be applied 'therapeutically' in existing disease states to alleviate symptoms and counter progression. ...
Cardiovascular disease, predominantly ischemic heart disease (IHD), is the leading cause of death in diabetes mellitus (DM). In addition to eliciting cardiomyopathy, DM induces a ‘wicked triumvirate’: (i) increasing the risk and incidence of IHD and myocardial ischemia; (ii) decreasing myocardial tolerance to ischemia–reperfusion (I–R) injury; and (iii) inhibiting or eliminating responses to cardioprotective stimuli. Changes in ischemic tolerance and cardioprotective signaling may contribute to substantially higher mortality and morbidity following ischemic insult in DM patients. Among the diverse mechanisms implicated in diabetic impairment of ischemic tolerance and cardioprotection, changes in sarcolemmal makeup may play an overarching role and are considered in detail in the current review. Observations predominantly in animal models reveal DM-dependent changes in membrane lipid composition (cholesterol and triglyceride accumulation, fatty acid saturation vs. reduced desaturation, phospholipid remodeling) that contribute to modulation of caveolar domains, gap junctions and T-tubules. These modifications influence sarcolemmal biophysical properties, receptor and phospholipid signaling, ion channel and transporter functions, contributing to contractile and electrophysiological dysfunction, cardiomyopathy, ischemic intolerance and suppression of protective signaling. A better understanding of these sarcolemmal abnormalities in types I and II DM (T1DM, T2DM) can inform approaches to limiting cardiomyopathy, associated IHD and their consequences. Key knowledge gaps include details of sarcolemmal changes in models of T2DM, temporal patterns of lipid, microdomain and T-tubule changes during disease development, and the precise impacts of these diverse sarcolemmal modifications. Importantly, exercise, dietary, pharmacological and gene approaches have potential for improving sarcolemmal makeup, and thus myocyte function and stress-resistance in this ubiquitous metabolic disorder.
... In summary, the available evidence does not suggest a strong anti- Table 5 Selection of intervention trials in adults with prebiotics or fibres and reporting on inflammatory outcomes. Roberts et al. (2006aRoberts et al. ( , 2006c Type 2 diabetic men Mean 64.6 (range 55-74); n = 13 3 week intervention with high fiber (> 40 g/day) and low fat diet ad libitum combined with physical activity CRP (↓19%), sICAM-1 (↓24%), sE-selectin (↓16%) Roberts et al. (2006b) Older community dwelling and/or nursing home subjects at risk of malnutrition Mean 84 (range 70-99); n = 74 12 week intervention with oral nutritional supplement containing fructooligosaccharides (1.95-3.9 g/day) sCD14 (↓14%) Schiffrin et al. (2007) Healthy men and postmenopausal women Mean 55.4 (range 50-70); n = 34 10 week intervention with 6 week intervention with raisins (1 cup/day) and/or additional walking (10-30 min/day) TNF-α (↓40%), sICAM-1 (↓, value not given) Puglisi et al. (2008) Obese and lean women Mean 55.4 (range 30-70); n = 35 5 different test meals in cross-over study with one meal rich in starch and fibers (19 g/meal) Post-prandial IL-6 (↓, value not given) in both obese and lean women Manning et al. (2008) Healthy postmenopausal women from Women's Health Initiative observational study Mean 62.2 (range 50-79); n = 1958 Association study relating serum inflammatory markers and dietary fiber intake (calculated based on FFQ analysis) IL-6 (↓ up to 22%) and sTNFRII (↓ up to 8%) for highest total fiber consumers (median value 24.7 g/day) Ma et al. (2008) Hypercholesterolemic In an ex vivo study, Heptinstall et al. (2006) showed inhibitory effects on leukocyte activation of four flavanol-rich cocoa beverages. ...
Ageing of the global population has become a public health concern with an important socio-economic dimension. Ageing is characterised by an increase in the concentration of inflammatory markers in the bloodstream, a phenomenon that has been termed "inflammageing". The inflammatory response is beneficial as an acute, transient reaction to harmful conditions, facilitating the defence, repair, turnover and adaptation of many tissues. However, chronic and low grade inflammation is likely to be detrimental for many tissues and for normal functions. We provide an overview of low grade inflammation (LGI) and determine the potential drivers and the effects of the "inflamed" phenotype observed in the elderly. We discuss the role of gut microbiota and immune system crosstalk and the gut-brain axis. Then, we focus on major health complications associated with LGI in the elderly, including mental health and wellbeing, metabolic abnormalities and infections. Finally, we discuss the possibility of manipulating LGI in the elderly by nutritional interventions. We provide an overview of the evidence that exists in the elderly for omega-3 fatty acid, probiotic, prebiotic, antioxidant and polyphenol interventions as a means to influence LGI. We conclude that slowing, controlling or reversing LGI is likely to be an important way to prevent, or reduce the severity of, age-related functional decline and the onset of conditions affecting health and well-being; that there is evidence to support specific dietary interventions as a strategy to control LGI; and that a continued research focus on this field is warranted.
Obesity is a constantly growing health problem which reduces quality of life and life expectancy. Bariatric surgery (BS) for obesity is considered when all other conservative treatment modalities have failed. Comparison of the multidisciplinary programs with BS regarding to the weight loss showed that substantial and durable weight reduction have been achieved only with bariatric surgical treatments. Although laparoscopic sleeve gastrectomy is the most popular BS, it has high long-term failure rates, and it is claimed that one of every three patients will undergo another bariatric procedure within a 10-year period. Although BS provides weight loss and improvement of metabolic comorbidities, in long-term follow-up, weight gain is observed in half of the patients, while decrease in bone mass and nutritional deficiencies occur in up to 90%. Moreover, despite significant weight loss, several psychological aspects of patients are worsened in comparison to preoperative levels. Nearly one-fifth of postoperative patients with “Loss-of-eating control” meet food addiction criteria. Therefore, the benefits of weight loss following bariatric procedures alone are still debated in terms of the proinflammatory and metabolic profile of obesity.
Objectives:
Although the physiological mechanisms are not fully understood, race/ethnicity differences vary across cardiometabolic disease risk factors. Resistance training (RT) is an effective therapy for improving these risk factors in addition to body composition and physical performance. Thus, the purpose of this study was to determine the effects of RT over time on different racial and ethnic populations across cardiometabolic, body composition, and physical performance outcomes.
Design:
Electronic databases Scopus and PubMed were searched for studies that compared different racial/ethnic responses to RT across cardiometabolic, body composition, and physical performance parameters. Inclusion criteria for the studies were as follows: (1) published in the English language; (2) compared races or ethnicities across cardiometabolic risk factors, body composition, or physical performance variables following a RT intervention; (3) included adults 18 years or older, and (4) included an isolated RT intervention group.
Results:
Nine studies were found that met the inclusion criteria. The identified studies involved cohorts of White American (WA), South Asian, European Chilean, Mapuche Chilean, White Scottish, and African American (AA) males and females. Race/ethnicity differences following a RT intervention were found for fat-free mass preservation and changes in blood pressure, endothelial function, brachial artery stiffness, cardiac autonomic function, inflammatory and oxidative stress markers, insulin sensitivity, body mass index, waist circumference, % body fat, and muscular strength. With the exception of changes in systolic blood pressure and brachial artery stiffness, AAs consistently showed more beneficial adaptations compared to WAs to RT across studies.
Conclusion:
Race and ethnicity play a role in how adults adapt to chronic RT. These data may aid in better understanding the social, biological, and environmental factors that likely influenced these racial/ethnic differences in response to RT, assist in creating tailored exercise prescriptions for various racial/ethnic populations, and inform policies for determining resource allocations to address health inequities.
Rheumatoid arthritis (RA) is a common systematic, chronic inflammatory, autoimmune, and polyarticular disease, causing a range of clinical manifestations, including joint swelling, redness, pain, stiffness, fatigue, decreased quality of life, progressive disability, cardiovascular problems, and other comorbidities. Strong evidence has shown that exercise is effective for RA treatment in various clinical domains. Exercise training for relatively longer periods (e.g., ≥ 12 weeks) can decrease disease activity of RA. However, the mechanism underlying the effectiveness of exercise in reducing RA disease activity remains unclear. This review first summarizes and highlights the effectiveness of exercise in RA treatment. Then, we integrate current evidence and propose biological mechanisms responsible for the potential effects of exercise on immune cells and immunity, inflammatory response, matrix metalloproteinases, oxidative stress, and epigenetic regulation. However, a large body of evidence was obtained from the non-RA populations. Future studies are needed to further examine the proposed biological mechanisms responsible for the effectiveness of exercise in decreasing disease activity in RA populations. Such knowledge will contribute to the basic science and strengthen the scientific basis of the prescription of exercise therapy for RA in the clinical routine.
Anxiety, depression, and stress are the most common psychological concerns among the population of society. The desirable changes in mental health are obtained through therapeutic diagnosis i.e., physical exercise practice and physical activity participation which are having a great potential as a prevention and treatment for these psychological issues. The purpose of the study was to systematically review the evidences for the effect of an exercise program on psychological variables i.e., anxiety, depression, and stress. For this purpose 198 research articles were reviewed from the available resources i.e. Research Gate, Pub Med, Google Scholar, Springer, Scopus, Web of Science and sample of 38 research articles were selected for the study as per the inclusion criteria. This study was given an idea that exercise interventions were beneficial in reducing the anxiety, depression, and stress. Further, research literature evidently reported that exercise in detention environments improves mental health. Findings of the study were concluded that low to high intensive exercise practices, physical activities and participation in recreational games brought the significant improvement in psychological variables i.e., anxiety, depression, and stress respectively in place of the alternative of drugs and other clinical treatment methods.
Purpose: Metabolic syndrome (MetS) is associated with poor prognosis in many cancers. However, few studies have comprehensively analyzed the relationship between metabolic syndrome and the overall survival of colorectal cancer (CRC) patients. Our study aimed to comprehensively analyze whether MetS could affect postoperative complications and long-term survival in patients with CRC.
Patients and methods: We included patients who underwent colorectal cancer resection at our center between January 2016 and December 2018 for this analysis. The propensity score matching analysis was performed to reduce the bias. Dividing CRC patients into MetS and Non-MetS groups based on whether they had MetS. Univariate and multivariate analyses were used to identify the risk factors affecting overall survival (OS).
Results: A total of 268 patients were included in the study, of whom 120 patients were included for further analysis after propensity score matching. No significant differences were found in Clinicopathological features between the MetS group and Non-MetS group after matching. Patients with MetS had a shorter OS compared with non-MetS (P=0.027), however the postoperative complications were not significantly different between them. In multivariate analysis, We found MetS (hazard ratio [HR]=1.997, P=0.042), tumor-node-metastasis (TNM) stage (HR=2.422, P=0.003), and intestinal obstruction (HR=2.761, P=0.010) were independent risk factors for OS.
Conclusion: Metabolic syndrome affects long-term survival of CRC patients without affecting postoperative complications.
A healthy plant-based diet (PBD), which consists of mostly plant-derived foods and abstains from animal products, has been shown to be effective in managing risk factors for cardiovascular disease (CVD) and in reducing adverse CVD outcomes. PBDs have been shown to have beneficial effects in the prevention of coronary artery disease, hypertension, cerebrovascular accident, type 2 diabetes mellitus, and heart failure and may also reduce cardiovascular mortality. Potential mechanisms for these benefits include reduction in atherogenic lipid levels (LDL-C and non-HDL-C), presence of anti-atherogenic compounds such as polyphenols and fibers, and avoidance of pro-atherogenic compounds found in animal products. Structured PBD/lifestyle programs have been developed, and while each varies in composition, all programs attempt to provide comprehensive recommendations for implementing a PBD to reduce CVD risk. Further research is needed to better understand the full range of benefits, and potential limitations, of a PBD and related structured diet/lifestyle programs. In clinical practice, recommendations for a healthy PBD should align with preferences of the individual patient in order to maximize both quality of life and cardiovascular benefit.
Objective
Metabolic syndrome (MetS) has previously been linked to increased risk of postoperative morbidity and mortality in other surgical undertakings. Because MetS is a consequence of endocrine dysfunction, and given the thyroid's crucial role in endocrine homeostasis, we sought to evaluate the association between MetS and postoperative outcomes of thyroidectomy.
Methods
Data were acquired from the ACS‐NSQIP database from years 2005 to 2017. Patients with obesity, diabetes, and hypertension were defined as having MetS. Odds ratios (OR) were obtained for outcomes to quantify risk with multivariate logistic regression.
Results
Outcomes significantly affected by MetS included overall complication (OR: 2.00), extended postoperative stay (OR: 1.52), medical complication (OR: 1.48), surgical complication (OR: 1.62), and mortality (OR: 2.33).
Conclusions
Patients with MetS undergoing thyroidectomy are at increased risk of an increased length of stay, overall complications, and mortality.
Psychosocial problems in adolescents
10 ،. ﺗﺎﺑﺴﺘﺎن 1390 ،. ﺻﺺ 32-13 ﻫﺰﻳﻨ از اﺳﺘﻔﺎده ﺑﺎ ﺑﺪﻧﻲ ﻓﻌﺎﻟﻴﺖ ﺳﻄﻮح ارزﻳﺎﺑﻲ ﺔ در روزاﻧﻪ اﻧﺮژي ﭘﺴﺮان 8 ﺗﺎ 16 ﻣﻨﻄﻘ ﻣﺪارس ﺳﺎل ﺔ ﻛﺸﻮر ﻏﺮب ﺷﻤﺎل دﻛﺘﺮ ﺗﺮﺗﻴﺒﻴﺎن ﺑﺨﺘﻴﺎر 1 ، ﺣﺎﺟﻲ ﺑﻬﺰاد ﻣﻠﻜﻲ زاده 2 ﻳﺎﻣﭽﻲ درﻓﺸﻲ ﺑﻬﺮوز ، 3 ﻓﻨﺎوري و ﺗﺤﻘﻴﻘﺎت ﻋﻠﻮم وزارت ورزﺷﻲ ﻋﻠﻮم و ﺑﺪﻧﻲ ﺗﺮﺑﻴﺖ ﭘﮋوﻫﺸﻜﺪه ﻣﻘﺎﻟﻪ درﻳﺎﻓﺖ ﺗﺎرﻳﺦ : 12 / 4 / 89 ﻣﻘﺎﻟﻪ ﭘﺬﻳﺮش ﺗﺎرﻳﺦ : 16 / 9 / 89 ﭼﻜﻴﺪه از اﺳﺘﻔﺎده ﺑﺎ ﺑﺪﻧﻲ ﻓﻌﺎﻟﻴﺖ ﺳﻄﻮح ارزﻳﺎﺑﻲ ﺣﺎﺿﺮ ﭘﮋوﻫﺶ ﻫﺪف اﻧﺮژي ﻫﺰﻳﻨﺔ ﭘﺴﺮان در روزاﻧﻪ 8 ﺗﺎ 16 ﺑﻮد ﻛﺸﻮر ﻏﺮب ﺷﻤﺎل ﻣﻨﻄﻘﻪ ﻣﺪارس ﺳﺎل. ﺗﻌﺪاد ﭘﮋوﻫﺶ اﻳﻦ در 2787 داﻧﺶ از ﻧﻔﺮ آﻣﻮزان 8 ﺗﺎ 16 ﻣﻨﻄﻘ ﻣﺪارس ﺳﺎل ﺔ ﺷﺮﻛﺖ ﻛﺸﻮر ﻏﺮب ﺷﻤﺎل ﻛﺮدﻧﺪ. ﻗﺪ) ﺳﺎﻧﺘﻲ ﻣﺘﺮ (وزن ،) ﻛﻴﻠﻮﮔﺮم (ﭼﺮﺑﻲ درﺻﺪ ، (%) ﺗﻮد ﺷﺎﺧﺺ ، ة ﺑﺪن) ﻛﻴﻠﻮﮔﺮم / ﻣﺘﺮﻣﺮﺑﻊ (ﻫﺰﻳﻨ و ﺔ روزاﻧﻪ اﻧﺮژي) ژول ﻛﻴﻠﻮ / ﺑﺪن وزن ﻛﻴﻠﻮﮔﺮم / روز (ﭘﺮﺳﺶ از اﺳﺘﻔﺎده ﺑﺎ ﻧﺎﻣ ﺔ ﻣﺒﻨﺎي ﺑﺮ ﺑﺪﻧﻲ ﻓﻌﺎﻟﻴﺖ ﺳﻄﻮح ارزﻳﺎﺑﻲ اﻧﺮژي ﻫﺰﻳﻨﺔ روزاﻧﻪ (QAPACE) اﻧﺪازه ﮔﻴﺮي ﺷﺪﻧﺪ. ﭘﺮﺳﺶ ﺗﻜﺮارﭘﺬﻳﺮي ﻧ آزﻣﻮن روش از اﺳﺘﻔﺎده ﺑﺎ ﺎﻣﻪ-ﮔﺮﻓﺖ اﻧﺠﺎم ﻣﺠﺪد آزﻣﻮن. آزﻣﻮن از ﻫﻤﭽﻨﻴﻦ ﻣﻘﺎﻳﺴ ﺑﺮاي ﻫﻤﺒﺴﺘﻪ ﺗﻲ آﻣﺎري ﻫﺎي ﺔ ﻫﻤﺒﺴﺘﮕﻲ ﻣﺨﺘﻠﻒ، زﻣﺎﻧﻲ ﻣﺮاﺣﻞ در ﻣﺘﻐﻴﺮﻫﺎ ﺧﻮﺷﻪ درون اي) ICC (ﺗﻌﻴﻴﻦ ﻫﻤﭽﻨﻴﻦ و ارزﻳﺎﺑﻲ ﺑﺮاي ﭘﻴﺮﺳﻮن ﻫﻤﺒﺴﺘﮕﻲ ﺿﺮﻳﺐ و رواﺋﻲ و اﻧﺪازه ﺗﻜﺮارﭘﺬﻳﺮي ﮔﻴﺮي ﺷﺪ اﺳﺘﻔﺎده ﻫﺎ. ﺿﺮﻳ ﺧﻮﺷﻪ درون ﻫﻤﺒﺴﺘﮕﻲ ﺐ در ﺑﺪن ﭼﺮﺑﻲ درﺻﺪ ﺑﺮاي اي ﮔﺮوه ﺳﻨﻲ ﻫﺎي 10-8 ، 13-11 و 16-14 ﺑﺎ ﺑﺮاﺑﺮ ﺗﺮﺗﻴﺐ ﺑﻪ ﺳﺎل 99 / 0 ، 99 / 0 و 99 / 0 ﻫﺰﻳﻨ ﺑﺮاي ، ﺔ اﻧﺮژي ﮔﺮوه در روزاﻧﻪ ﺳﻨﻲ ﻫﺎي 10-8 ، 13-11 و 16-14 ﺑﺎ ﺑﺮاﺑﺮ ﺗﺮﺗﻴﺐ ﺑﻪ ﺳﺎل 98 / 0 ، 98 / 0 و 99 / 0 ﺑﺮاي و ﺗﻮد ﺷﺎﺧﺺ ة ﮔﺮوه در ﺑﺪﻧﻲ ﺳﻨﻲ ﻫﺎي 10-8 ، 13-11 و 16-14 ﺑﺎ ﺑﺮاﺑﺮ ﺗﺮﺗﻴﺐ ﺑﻪ ﺳﺎل 00 / 1 ، 00 / 1 و 00 / 1 ﺑﻮد. ﻣﻄﺎﻟﻌ ﻧﺘﺎﻳﺞ ﻫﻤﭽﻨﻴﻦ ﺔ ﻫﺰﻳﻨ ﻣﺘﻮﺳﻂ ﻣﻴﺰان ﻛﻪ داد ﻧﺸﺎن ﺣﺎﺿﺮ ﺔ داﻣﻨ اﻓﺰاﻳﺶ ﺑﺎ روزاﻧﻪ اﻧﺮژي ﺔ ﺗﻐﻴﻴﺮ ﺳﻨﻲ ي دا ﻣﺤﺴﻮس رد) 05 / 0 P≤ (ﺑﻪ ﭘﺴﺮان ﻛﻪ ﻃﻮري داﻣﻨ ﺑﺎ ﺔ ﺳﻨﻲ 10-8 ﻓﻌﺎل ﺳﺎل از ﺗﺮ داﻣﻨ ﺑﺎ ﭘﺴﺮان ﺔ ﺳﻨﻲ 13-11 و 16-14 ﺑﻮدﻧﺪ ﺳﺎل. ﺑ ﻪ ﮔﺮوه در ﻋﻼوه، ﺳﻨﻲ ﻫﺎي 10-8 ، 13-11 و 16-14 ﻣﺘﻮﺳﻂ ﺳﺎل، اﻧﺮژي ﻫﺰﻳﻨﺔ ﺑﺮاﺑﺮ ﺗﺮﺗﻴﺐ ﺑﻪ روزاﻧﻪ 131 ، 4 / 120 و 85 / 121 وزن ﻛﻴﻠﻮﮔﺮم در ﻛﻴﻠﻮژول ﻣﺘﻮﺳﻂ ﺳﻄﺢ از ﻛﻪ ﺑﻮد روز در ﺑﺪن ﻧﺮم ﺑﻴﻦ اﻟﻠﻤﻠﻲ) ﺳﻄﺢ در 50 ﺗﺮﺗﻴﺐ ﺑﻪ درﺻﺪ 138 ، 124 و 136 ﻛﻴ در ﻛﻴﻠﻮژول در ﺑﺪن وزن ﻠﻮﮔﺮم روز (ﭘﺎﻳﻴﻦ ﺑﻮد ﺗﺮ. ﻧﺸﺎن ﺣﺎﺿﺮ ﭘﮋوﻫﺸﻲ ﻃﺮح ﻧﺘﺎﻳﺞ ﻣﺠﻤﻮع، در ﻣﻲ داﻧﺶ ﻛﻪ دﻫﺪ اﺳﺘﺎﻧﺪارد ﻣﻘﺎدﻳﺮ ﺑﻪ ﻧﺴﺒﺖ ﺳﻨﻲ، ﮔﺮوه ﺳﻪ ﻫﺮ در آﻣﻮزان اﻧﺮژي ﻫﺰﻳﻨﺔ از روزاﻧﻪ ﭘﺎﻳﻴﻦ ﻣﻘﺎدﻳﺮ اﻧﺮژي ﻫﺰﻳﻨﺔ ﭘﺮﺳﺶ و ﺑﺮﺧﻮردارﻧﺪ روزاﻧﻪ از ﺣﺎﺿﺮ ﭘﮋوﻫﺶ در ﺷﺪه اﺳﺘﻔﺎده ﻧﺎﻣﻪ ﺗﻜﺮارﭘﺬﻳﺮي از اﺳﺘﻔﺎده ﺑﺎ ﺑﺪﻧﻲ ﻓﻌﺎﻟﻴﺖ ﺳﻄﻮح ارزﻳﺎﺑﻲ ﺑﺮاي ﻣﻄﻠﻮب اﻧﺮژي ﻫﺰﻳﻨﺔ ﭘﺴﺮان در روزاﻧﻪ 8 ﺗﺎ 16 ﻣﻨﻄﻘ ﻣﺪارس ﺳﺎل ﺔ ﻣﻲ ﺑﺮﺧﻮردار ﻛﺸﻮر ﻏﺮب ﺷﻤﺎل ﺑﺎﺷﺪ. ﻛﻠﻴﺪ واژه ﻫﺎي ﻓﺎرﺳﻲ : ﻫﺰﻳﻨ ﭘﺴﺮان، ﺔ ﭘﺮﺳﺶ روزاﻧﻪ، اﻧﺮژي رواﺋﻲ ﻧﺎﻣﻪ، ﺳﻨﺠﻲ .
Background and aims
Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD.
Methods and Results
We enrolled patients with moderate to severe CKD through a multi-center pilot randomized trial of diet and exercise in a 4-arm design (dietary restriction of 10%-15% reduction in caloric intake, exercise three times/week, combined diet and exercise, and control) (NCT01150851). Adipocytokines (adiponectin and leptin) were measured at the beginning and end of the study period as secondary outcomes. Treatment effect was analyzed in a multivariable model adjusted for baseline outcome values, age, gender, site and diabetes. A total of 122 participants were consented, 111 were randomized (42% female, 25% diabetic, and 91% hypertensive), 104 started intervention and 92 completed the study (Figure 1). Plasma adiponectin levels increased significantly in response to diet by 23% (95% CI: 0.2%, 49.8%, p=0.048) among participants randomized to the caloric restriction and usual activity arm but not to exercise, whereas circulating leptin did not change by either treatment.
Conclusion
Our data suggest that dietary caloric restriction increases plasma adiponectin levels in stage 3-4 CKD patients, with limited effect on leptin levels. These findings suggest the potential for improving the metabolic milieu of CKD with moderate calorie restriction.
Objective:
To examine if peroxiredoxin 2 (Prx2) deficiency aggravates high-fat diet-induced insulin resistance.
Material and methods:
Insulin sensitivity was measured in Prx2 knockout (KO) and wild-type (WT) littermates using the hyperinsulinemic-euglycemic clamp.
Results:
Whole body glucose turnover, glucose uptake, and levels of glucose transporter 4 (Glut4) protein in the skeletal muscle were found to be lower. This was followed by increased expression of oxidative stress markers in Prx2 KO mice than that in WT mice in the control diet group. Although, a 12-week high-fat diet induced insulin resistance and enhanced oxidative stress in both genotypes, there was no difference between WT and Prx2 KO mice with respect to insulin sensitivity and the level of oxidative stress markers. Accordingly, the levels of phosphorylated Akt and Glut4 were similar between the two genotypes.
Conclusion:
These results suggest that Prx2 does not affect high-fat diet-induced oxidative stress and insulin resistance in mice.
Background:
Metabolic syndrome is associated with poorer postoperative outcomes after various abdominal operations. However, the impact of metabolic syndrome on outcomes after colorectal cancer surgery remains poorly described.
Objective:
The purpose of this study was to determine the association between metabolic syndrome and short-term postoperative outcomes in patients undergoing elective colorectal cancer surgery.
Design:
This was a retrospective cohort study.
Settings:
This study used a national multicenter database.
Patients:
Adult patients who underwent elective colectomy for colorectal cancer from 2010 to 2016 were identified in the American College of Surgeons National Surgical Quality Improvement Program database.
Main outcome measures:
Thirty-day postoperative mortality and morbidity, unplanned reoperation, unplanned readmission, operative time, and length of stay were measured.
Results:
A total of 91,566 patients were analyzed; 7603 (8.3%) had metabolic syndrome. On unadjusted analysis, metabolic syndrome was associated with an increased risk of 30-day overall morbidity, pulmonary complications, renal complications, septic complications, cardiac complications, wound complications, blood transfusion, longer length of stay, and unplanned readmissions. On multivariable analysis, metabolic syndrome remained significantly associated with renal complications (OR = 1.44 (95% CI, 1.29-1.60)), superficial surgical site infection (OR = 1.46 (95% CI, 1.32-1.60)), deep surgical site infection (OR = 1.40 (95% CI, 1.15-1.70)), wound dehiscence (OR = 1.47 (95% CI, 1.20-1.80)), and unplanned readmissions (HR = 1.24 (95% CI, 1.15-1.34)). The risks of overall morbidity, cardiac and septic complications, and prolonged length of stay for laparoscopic procedures were significantly associated with diabetes mellitus rather than metabolic syndrome as a composite entity.
Limitations:
This study was limited by its retrospective design and inability to analyze outcomes beyond 30 days.
Conclusions:
Patients with metabolic syndrome undergoing elective surgery for colorectal cancer have an increased risk of 30-day postoperative renal complications, wound complications, and unplanned hospital readmissions. A multidisciplinary approach involving lifestyle modifications and pharmacologic interventions to improve the components of metabolic syndrome should be implemented preoperatively for these patients. See Video Abstract at http://links.lww.com/DCR/A909.
Abstract:
Aging and menopause lead to various chronic diseases in women. Regular physical exercise improves metabolic disorders, cardiovascular diseases and inflammatory markers. The aim of this study was to investigate the effect of 8 weeks of circuit resistance training on the oxidative low density lipoprotein (Ox-LDL), high sensitive C reactive protein (CRP), glycosylated hemoglobin (HbA1c) and insulin resistance index (HOMA-IR) in sedentary postmenopausal women.29 sedentary postmenopausal women (age=55.83±4.33 years) were selected randomly from volunteers. Subjects were divided into two groups: a group with 15 patients (BMI=31.81±4.90 kg/m2) and a control group with 14 patients (BMI=30.22±3.78 kg/m2). The training program included an eight-week circuit resistance training conducted 3 sessions a week (60-90 minutes per session) with an intensity of %60-%75 of the maximum 1RM. For data analysis, the independent and dependent t tests were used. Significance level was set at P<0.05. Data were analyzed by SPSS20 software. After 8 weeks, fasting glucose (P=0.035), insulin resistance index (P=0.05), hs-CRP (P=0.042), total cholesterol (P=0.035), triglycerides (P=0.040), LDL-C (P=0.01) and uric acid (P=0.012) significantly decreased in the resistance training group. Also, there was a significant difference between hs-CRP and LDL-C in both groups. According to the results, it seems that circuit resistance training can reduce the causes of metabolic and cardiovascular disorders and immune function in postmenopausal women.
Keyword(s): CIRCUIT RESISTANCE TRAINING, INSULIN RESISTANCE INDEX, HS-CRP, HBA1C, SEDENTARY POSTMENOPAUSAL WOMEN
Objective:
Phagocyte-derived myeloperoxidase (MPO) and proinflammatory HDL are associated with metabolic syndrome (MetS) and increased cardiovascular disease risk. Therapeutic lifestyle changes (TLCs), such as a Mediterranean diet and exercise, decrease this risk. However, the link among TLCs, HDL, and MPO-mediated oxidative stress remains unclear.
Research design and methods:
In this study, we characterized changes in cholesterol efflux capacity (CEC), a metric of HDL function; MPO-mediated oxidation; and the HDL proteomic profile in 25 patients with MetS who underwent 12 weeks of TLCs.
Results:
After 12 weeks, before significant changes to HDL levels, most MetS components improved as a result of the TLCs. CEC was significantly increased, and HDL MPO oxidation products, 3-chlorotyrosine and 3-nitrotyrosine, were decreased with TLCs. The changes in CEC were inversely related to the unit changes in 3-chlorotyrosine after we controlled for changes in the other MetS components. TLCs did not remodel the HDL proteome.
Conclusions:
In summary, TLCs improved HDL function by inhibiting MPO-mediated oxidative stress even before appreciable changes in HDL levels.
Purpose: Selections are a family of cell adhesion molecules that are responsible for adhesion of leukocytes to the endothelium and commencement of atherogenic processes. The purpose of this study was to analyze the effect of eight weeks high intensity interval training on the levels of E-selection and P-selection. Methods: 16 obese young females were randomly assigned into two experimental (N=8, age; 26.12±3.1 years; height, 1.6±0.06 meters; weight, 85.5±16.6 kilograms) and control groups (n=8; age, 31±6.23 years; height, 1.6±0.02 meters; weight, 76.2±12.06 kilograms). Exercise protocol included eight weeks (three sessions per week, each session four to seven repetitions of running with maximum velocity in a 40 meters distance with 30 seconds' recovery) HIIT trainings. Fasting blood samples were taken 24h before and after the training. Elisa method was used to measure the dependent variables. Results: Analysis of data using student T-test showed no significant changes in the levels of E-selection and P-selection after trainings (P>0.05). Conclusion: It was concluded that more duration of training is probably needed to have significant effect of HIIT trainings on the levels of E-selection and P-selection.
Exercise training prevents the onset and the development of many chronic diseases, acting as an effective tool both for primary and for secondary prevention. Various mechanisms that may be the effectors of these beneficial effects have been proposed during the past decades: some of these are well recognized, others less. Muscular myokines, released during and after muscular contraction, have been proposed as key mediators of the systemic effects of the exercise. Nevertheless the availability of an impressive amount of evidence regarding the systemic effects of muscle-derived factors, few studies have examined key issues: (I) if skeletal muscle cells themselves are the main source of cytokine during exercise; (II) if the release of myokines into the systemic circulation reach an adequate concentration to provide significant effects in tissues far from skeletal muscle; (III) what may be the role carried out by muscular cytokine regarding the well-known benefits induced by regular exercise, first of all the anti-inflammatory effect of exercise. Furthermore, a greater part of our knowledge regarding myokines derives from the muscle of healthy subjects. This knowledge may not necessarily be transferred per se to subjects with chronic diseases implicating a direct or indirect muscular dysfunction and/or a chronic state of inflammation with persistent immune-inflammatory activation (and therefore increased circulating levels of some cytokines): cachexia, sarcopenia due to multiple factors, disability caused by neurological damage, chronic congestive heart failure (CHF) or coronary artery disease (CAD). A key point of future studies is to ascertain how is modified the muscular release of myokines in different categories of unhealthy subjects, both at baseline and after rehabilitation. The purpose of this review is to discuss the main findings on the role of myokines as putative mediators of the therapeutic benefits obtained through regular exercise in the context of secondary cardiovascular prevention.
Introduction: Selectin molecules are responsible for leukocyte adhesion to vascular endothelium. We evaluated the effects of eight weeks high-intensity interval training (HIIT) on Eselectin and P- selectin in obese women. Materials and Methods: In this quasi-experimental study, 16 obese women participants (age: 28.06±3.62 years, BMI: 31.49±5.15 kg/m2) using the convenience sampling method, were randomly categorized into two groups (n=8 each), the experimental and the controls. In the trained group, the volunteers participated in 8 weeks HIIT, 3 days/week the HIIT program training included: 45-60 min duration with 90% HRR per session. The Rockport test was used to estimate maximal oxygen consumption. Blood samples were taken from the participants at the beginning end of 8 weeks in order to measure factors such as (E-selectin and P- selectin). Data were analyzed using paired and independent sample t-test for comparison of means within and between groups respectively, with level of significance set at p:0.05. Results: Weight and BMI levels reduced, although changes were not significant. WHR reduced significantly at the end of the 8 week period (p=0.007) and Vo2max increased significantly. (p=0.00). In the aerobic exercise group, E-selectin decreased from 89.76 to 84.27 ng per ml and P-selectin from 7.88 to 7.47 ng per ml, again the difference not statistically significant (p>0.05). Conclusion: Considering reduction in weight and selectin molecules and increased Vo2max, following HIIT training, this can be used in as therapy for management of cardiovascular patients.
The oxidative conversion of LDL into an atherogenic form is considered a pivotal event in the development of cardiovascular disease. Recent studies have identified reactive nitrogen species generated by monocytes by way of the myeloperoxidase-hydrogen peroxide-nitrite (MPO-H2O2-NO2-) system as a novel mechanism for converting LDL into a high-uptake form (NO2-LDL) for macrophages. We now identify the scavenger receptor CD36 as the major receptor responsible for high-affinity and saturable cellular recognition of NO2-LDL by murine and human macrophages. Using cells stably transfected with CD36, CD36-specific blocking mAbs, and CD36-null macrophages, we demonstrated CD36-dependent binding, cholesterol loading, and macrophage foam cell formation after exposure to NO2-LDL. Modification of LDL by the MPO-H2O2- NO2-system in the presence of up to 80% lipoprotein-deficient serum (LPDS) still resulted in the conversion of the lipoprotein into a high-uptake form for macrophages, whereas addition of less than 5% LPDS totally blocked Cu2+-catalyzed LDL oxidation and conversion into a ligand for CD36. Competition studies demonstrated that lipid oxidation products derived from 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine can serve as essential moieties on NO2-LDL recognized by CD36. Collectively, these results suggest that MPO-dependent conversion of LDL into a ligand for CD36 is a likely pathway for generating foam cells in vivo. MPO secreted from activated phagocytes may also tag phospholipid-containing targets for removal by CD36- positive cells.
Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2-fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1-fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from the cocultures that had been incubated with LDL induced target endothelial cells (EC) to bind monocyte but not neutrophil-like cells. Media collected from cocultures that had been incubated with LDL-induced monocyte migration into the subendothelial space of other cocultures that had not been exposed to LDL. In contrast, media from separate cultures of EC or smooth muscle cells (SMC) containing equal number of EC or SMC compared to coculture and incubated with the same LDL did not induce monocyte migration when incubated with the target cocultures. High density lipoprotein HDL, when presented to cocultures together with LDL, reduced the increased monocyte transmigration by 91%. Virtually all of the HDL-mediated inhibition was accounted for by the HDL2 subfraction. HDL3 was essentially without effect. Apolipoprotein AI was also ineffective in preventing monocyte transmigration while phosphatidylcholine liposomes were as effective as HDL2 suggesting that lipid components of HDL2 may have been responsible for its action. Preincubating LDL with beta-carotene or with alpha-tocopherol did not reduce monocyte migration. However, pretreatment of LDL with probucol or pretreatment of the cocultures with probucol, beta-carotene, or alpha-tocopherol before the addition of LDL prevented the LDL-induced monocyte transmigration. Addition of HDL or probucol to LDL after the exposure to cocultures did not prevent the modified LDL from inducing monocyte transmigration in fresh cocultures. We conclude that cocultures of human aortic cells can modify LDL even in the presence of serum, resulting in the induction of MCP-1, and that HDL and antioxidants prevent the LDL induced monocyte transmigration.
A modification of the method for monocyte isolation reported by Recalde (1984. J. Immunol. Methods. 69: 71-77) is described. Application of the modified method to 36 consecutive healthy adult donors gave a monocyte purity of 73 +/- 8% monocytes with less than 1% polymorphonuclear leukocytes and a yield of 3.44 +/- 0.93 x 10(5) monocytes/ml blood. While the monocyte purity of the modified Recalde method was lower than that obtained by elutriation (method BB in Fogelman et al. 1981. J. Lipid Res. 22: 1131-1141) in 15 donors (71 +/- 10% vs. 83 +/- 6%) the monocyte yield and the viability of the cells before and after culture were similar in both methods. The modified Recalde method does not require the expensive or complicated equipment required for elutriation and permits the isolation of human monocytes for culture in autologous serum from multiple donors in a single day.
We have developed a quantitative assay to monitor the oxidative burst (H2O2 production) of polymorphonuclear leukocytes (PMNL) using single cell analysis by flow cytometry, and have examined whether PMNL respond to membrane stimulation with an all-or-none oxidative burst. During incubation with normal neutrophils, dichlorofluorescin diacetate diffused into the cells, was hydrolyzed to 2',7'-dichlorofluorescin (DCFH) and was thereby trapped within the cells. The intracellular DCFH, a nonfluorescent fluorescein analogue, was oxidized to highly fluorescent 2',7'-dichlorofluorescein (DCF) by PMNL stimulated by phorbol myristate acetate (PMA). That the oxidative product was DCF was shown by excitation/emission spectra and by mass spectrometry of the product from PMA-stimulated PMNL. Normal resting and PMA-stimulated PMNL oxidized 6.9 +/- 0.7 and 160 +/- 13 attomoles DCF per cell, respectively, in 15 min. Absence of calcium and magnesium ions and/or addition of 2 mM EDTA did not inhibit DCF formation by PMNL stimulated by 100 ng/ml PMA. Since EDTA prevented aggregation of PMNL (even when stimulated by 100 ng/ml PMA), which would prevent accurate flow cytometric analysis, further experiments were performed with EDTA in the medium. A close correlation between average DCFH oxidation and hexose monophosphate shunt stimulation was demonstrated using cells from patients whose PMNL had oxidative metabolic defects of varying severity. Intracellular DCFH was also oxidized by reagent H2O2 or oxygen derivatives generated by glucose oxidase + glucose or by xanthine oxidase + acetaldehyde; DCFH oxidation by these systems was inhibited by catalase but unchanged by superoxide dismutase. The data indicate that the DCFH oxidation assay is quantitatively related to the oxidative metabolic burst of PMNL, and they strongly suggest that the reaction is mediated by H2O2 generated by the PMNL. Incubation of PMNL with varying concentrations of PMA caused graded responses by all PMNL present; i.e., 1 ng/ml PMA caused a mean response of 34% maximal with a single population of responding PMNL (rather than 66% resting and 34% fully stimulated as predicted by the all-or-none hypothesis). Thus, with these assay conditions, oxidative product formation by PMNL occurs as a graded response to membrane stimulation by PMA.
Oxidatively modified lipoproteins have been implicated in atherogenesis, but the mechanisms that promote oxidation in vivo have not been identified. Myeloperoxidase, a heme protein secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins in vitro. To explore the potential role of myeloperoxidase in the development of atherosclerosis, we determined whether the enzyme was present in surgically excised human vascular tissue. In detergent extracts of atherosclerotic arteries subjected to Western blotting, a rabbit polyclonal antibody monospecific for myeloperoxidase detected a 56-kD protein, the predicted molecular mass of the heavy subunit. Both the immunoreactive protein and authentic myeloperoxidase bound to a lectin-affinity column; after elution with methyl mannoside their apparent molecular masses were indistinguishable by nondenaturing size-exclusion chromatography. Peroxidase activity in detergent extracts of atherosclerotic lesions likewise bound to a lectin column and eluted with methyl mannoside. Moreover, eluted peroxidase generated the cytotoxic oxidant hypochlorous acid (HOCl), indicating that enzymatically active myeloperoxidase was present in lesions. Patterns of immunostaining of arterial tissue with antihuman myeloperoxidase antibodies were similar to those produced by an antimacrophage antibody, and were especially prominent in the shoulder region of transitional lesions. Intense foci of myeloperoxidase immunostaining also appeared adjacent to cholesterol clefts in lipid-rich regions of advanced atherosclerotic lesions. These findings identify myeloperoxidase as a component of human vascular lesions. Because this heme protein can generate reactive species that damage lipids and proteins, myeloperoxidase may contribute to atherogenesis by catalyzing oxidative reactions in the vascular wall.
We previously reported that high density lipoprotein (HDL) protects against the oxidative modification of low density lipoprotein (LDL) induced by artery wall cells causing these cells to produce pro-inflammatory molecules. We also reported that enzyme systems associated with HDL were responsible for this anti-inflammatory property of HDL. We now report studies comparing HDL before and during an acute phase response (APR) in both humans and a croton oil rabbit model. In rabbits, from the onset of APR the protective effect of HDL progressively decreased and was completely lost by day three. As serum amyloid A (SAA) levels in acute phase HDL (AP-HDL) increased, apo A-I levels decreased 73%. Concomitantly, paraoxonase (PON) and platelet activating factor acetylhydrolase (PAF-AH) levels in HDL declined 71 and 90%, respectively, from days one to three. After day three, there was some recovery of the protective effect of HDL. AP-HDL from human patients and rabbits but not normal or control HDL (C-HDL) exhibited increases in ceruloplasmin (CP). This increase in CP was not seen in acute phase VLDL or LDL. C-HDL incubated with purified CP and re-isolated (CP-HDL), lost its ability to inhibit LDL oxidation. Northern blot analyses demonstrated enhanced expression of MCP-1 in coculture cells treated with AP-HDL and CP-HDL compared to C-HDL. Enrichment of human AP-HDL with purified PON or PAF-AH rendered AP-HDL protective against LDL modification. We conclude that under basal conditions HDL serves an anti-inflammatory role but during APR displacement and/or exchange of proteins associated with HDL results in a pro-inflammatory molecule.
Nitric oxide (.NO) plays a central role in the pathogenesis of diverse inflammatory and infectious disorders. The toxicity of .NO is thought to be engendered, in part, by its reaction with superoxide (O2.-), yielding the potent oxidant peroxynitrite (ONOO-). However, evidence for a role of ONOO- in vivo is based largely upon detection of 3-nitrotyrosine in injured tissues. We have recently demonstrated that nitrite (NO2-), a major end-product of .NO metabolism, readily promotes tyrosine nitration through formation of nitryl chloride (NO2Cl) and nitrogen dioxide (.NO2) by reaction with the inflammatory mediators hypochlorous acid (HOCl) or myeloperoxidase. We now show that activated human polymorphonuclear neutrophils convert NO2- into NO2Cl and .NO2 through myeloperoxidase-dependent pathways. Polymorphonuclear neutrophil-mediated nitration and chlorination of tyrosine residues or 4-hydroxyphenylacetic acid is enhanced by addition of NO2- or by fluxes of .NO. Addition of 15NO2- led to 15N enrichment of nitrated phenolic substrates, confirming its role in polymorphonuclear neutrophil-mediated nitration reactions. Polymorphonuclear neutrophil-mediated inactivation of endothelial cell angiotensin-converting enzyme was exacerbated by NO2-, illustrating the physiological significance of these reaction pathways to cellular dysfunction. Our data reveal that NO2- may regulate inflammatory processes through oxidative mechanisms, perhaps by contributing to the tyrosine nitration and chlorination observed in vivo.
Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease.
We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography.
In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group).
Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.
Apolipoprotein A-I (apoA-I) and an apoA-I peptide mimetic removed seeding molecules from human low density lipoprotein (LDL) and rendered the LDL resistant to oxidation by human artery wall cells. The apoA-I-associated seeding molecules included hydroperoxyoctadecadienoic acid (HPODE) and hydroperoxyeicosatetraenoic acid (HPETE). LDL from mice genetically susceptible to fatty streak lesion formation was highly susceptible to oxidation by artery wall cells and was rendered resistant to oxidation after incubation with apoA-I in vitro. Injection of apoA-I (but not apoA-II or murine serum albumin) into mice rendered their LDL resistant to oxidation within 3 h. Infusion of apoA-I into humans rendered their LDL resistant to oxidation within 6 h. We conclude that 1) oxidation of LDL by artery wall cells requires seeding molecules that include HPODE and HPETE; 2) LDL from mice genetically susceptible to atherogenesis is more readily oxidized by artery wall cells; and 3) normal HDL and its components can remove or inhibit the activity of lipids in freshly isolated LDL that are required for oxidation by human artery wall cells.
Myeloperoxidase uses hydrogen peroxide (H2O2) to generate hypochlorous acid (HOCl), a potent cytotoxic oxidant. We demonstrate that HOCl regulates the activity of matrix metalloproteinase-7 (MMP-7, matrilysin) in vitro, suggesting that this oxidant activates MMPs in the artery wall. Indeed, both MMP-7 and myeloperoxidase were colocalized to lipid-laden macrophages in human atherosclerotic lesions. A highly conserved domain called the cysteine switch has been proposed to regulate MMP activity. When we exposed a synthetic peptide that mimicked the cysteine switch to HOCl, HPLC analysis showed that the thiol residue reacted rapidly, generating a near-quantitative yield of products. Tandem mass spectrometric analysis identified the products as sulfinic acid, sulfonic acid, and a dimer containing a disulfide bridge. In contrast, the peptide reacted slowly with H2O2, and the only product was the disulfide. Moreover, HOCl markedly activated pro-MMP-7, an MMP expressed at high levels in lipid-laden macrophages in vivo. Tandem mass spectrometric analysis of trypsin digests revealed that the thiol residue of the enzyme's cysteine switch domain had been converted to sulfinic acid. Thiol oxidation was associated with autolytic cleavage of pro-MMP-7, strongly suggesting that oxygenation activates the latent enzyme. In contrast, H2O2 failed to oxidize the thiol residue of the protein or activate the enzyme. Thus, HOCl activates pro-MMP-7 by converting the thiol residue of the cysteine switch to sulfinic acid. This activation mechanism is distinct from the well-studied proteolytic cleavage of MMP pro-enzymes. Our observations raise the possibility that HOCl generated by myeloperoxidase contributes to MMP activation, and therefore to plaque rupture, in the artery wall. HOCl and other oxidants might regulate MMP activity by the same mechanism in a variety of inflammatory conditions.
Background The finding that expression of metalloproteinases (MMPs) is induced in atherosclerotic plaques prone to rupture suggests the possibility that patients with atherosclerotic diseases would show enhanced blood levels of MMPs and that MMPs might represent a potential inflammatory risk factor for atherosclerosis. Therefore, the present study was aimed at verifying whether MMPs may represent sensitive markers of inflammation in patients with coronary artery disease.
Methods MMP-2, MMP-9, interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen levels were measured in blood samples obtained from 66 cases with previous acute myocardial infarction and 66 control subjects similar for age, sex, and major atherosclerotic risk factors but without history or evidence of atherothrombotic diseases.
Results Biohumoral markers of inflammation and MMP-9 levels were significantly elevated in cases compared with controls (median values 40.6 versus 9.8 ng/mL; p < .0001), whereas MMP-2 levels did not differ between the two groups (median values 839 versus 873 ng/mL; p = .53). A direct correlation was found among MMP-9, CRP, IL-6, and fibrinogen levels. Conditional logistic regression analysis showed that MMP-9 is related to myocardial infarction (p = .006) even after adjusting for cardiovascular medications and CRP.
Conclusion These findings suggest that measurement of serum MMP-9 levels may represent a novel marker of inflammation in patients with known coronary artery disease and might provide an index of plaque activity in this clinical setting.
Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis. Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients. Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage. In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors. Moreover, certain treatments that reduce coronary risk also limit inflammation. In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels. These new insights into inflammation in atherosclerosis not only increase our understanding of this disease, but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
Context The Third Report of the National Cholesterol Education Program Expert
Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults (ATP III) highlights the importance of treating patients with the metabolic
syndrome to prevent cardiovascular disease. Limited information is available
about the prevalence of the metabolic syndrome in the United States, however.Objective To estimate the prevalence of the metabolic syndrome in the United States
as defined by the ATP III report.Design, Setting, and Participants Analysis of data on 8814 men and women aged 20 years or older from the
Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional
health survey of a nationally representative sample of the noninstitutionalized
civilian US population.Main Outcome Measures Prevalence of the metabolic syndrome as defined by ATP III (≥3 of
the following abnormalities): waist circumference greater than 102 cm in men
and 88 cm in women; serum triglycerides level of at least 150 mg/dL (1.69
mmol/L); high-density lipoprotein cholesterol level of less than 40 mg/dL
(1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of
at least 130/85 mm Hg; or serum glucose level of at least 110 mg/dL (6.1 mmol/L).Results The unadjusted and age-adjusted prevalences of the metabolic syndrome
were 21.8% and 23.7%, respectively. The prevalence increased from 6.7% among
participants aged 20 through 29 years to 43.5% and 42.0% for participants
aged 60 through 69 years and aged at least 70 years, respectively. Mexican
Americans had the highest age-adjusted prevalence of the metabolic syndrome
(31.9%). The age-adjusted prevalence was similar for men (24.0%) and women
(23.4%). However, among African Americans, women had about a 57% higher prevalence
than men did and among Mexican Americans, women had about a 26% higher prevalence
than men did. Using 2000 census data, about 47 million US residents have the
metabolic syndrome.Conclusions These results from a representative sample of US adults show that the
metabolic syndrome is highly prevalent. The large numbers of US residents
with the metabolic syndrome may have important implications for the health
care sector.
Background— Inflammation plays a pivotal role in atherosclerosis. In addition to being a risk marker for cardiovascular disease, much recent data suggest that C-reactive protein (CRP) promotes atherogenesis via effects on monocytes and endothelial cells. The metabolic syndrome is associated with significantly elevated levels of CRP. Plasminogen activator inhibitor-1 (PAI-1), a marker of atherothrombosis, is also elevated in the metabolic syndrome and in diabetes, and endothelial cells are the major source of PAI-1. However, there are no studies examining the effect of CRP on PAI-1 in human aortic endothelial cells (HAECs).
Methods and Results— Incubation of HAECs with CRP results in a time- and dose-dependent increase in secreted PAI-1 antigen, PAI-1 activity, intracellular PAI-1 protein, and PAI-1 mRNA. CRP stabilizes PAI-1 mRNA. Inhibitors of endothelial NO synthase, blocking antibodies to interleukin-6 and an endothelin-1 receptor blocker, fail to attenuate the effect of CRP on PAI-1. CRP additionally increased PAI-1 under hyperglycemic conditions.
Conclusions— This study makes the novel observation that CRP induces PAI-1 expression and activity in HAECs and thus has implications for both the metabolic syndrome and atherothrombosis. (Circulation. 2003;107:398-404.)
Received November 14, 2002; revision received December 3, 2002; accepted December 4, 2002.
The finding that expression of metalloproteinases (MMPs) is induced in atherosclerotic plaques prone to rupture suggests the possibility that patients with atherosclerotic diseases would show enhanced blood levels of MMPs and that MMPs might represent a potential inflammatory risk factor for atherosclerosis. Therefore, the present study was aimed at verifying whether MMPs may represent sensitive markers of inflammation in patients with coronary artery disease.
MMP-2, MMP-9, interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen levels were measured in blood samples obtained from 66 cases with previous acute myocardial infarction and 66 control subjects similar for age, sex, and major atherosclerotic risk factors but without history or evidence of atherothrombotic diseases.
Biohumoral markers of inflammation and MMP-9 levels were significantly elevated in cases compared with controls (median values 40.6 versus 9.8 ng/mL; p < .0001), whereas MMP-2 levels did not differ between the two groups (median values 839 versus 873 ng/mL; p = .53). A direct correlation was found among MMP-9, CRP, IL-6, and fibrinogen levels. Conditional logistic regression analysis showed that MMP-9 is related to myocardial infarction (p = .006) even after adjusting for cardiovascular medications and CRP.
These findings suggest that measurement of serum MMP-9 levels may represent a novel marker of inflammation in patients with known coronary artery disease and might provide an index of plaque activity in this clinical setting.
LR: 20061115; JID: 7501160; 0 (Antilipemic Agents); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 57-88-5 (Cholesterol); CIN: JAMA. 2001 Nov 21;286(19):2401; author reply 2401-2. PMID: 11712930; CIN: JAMA. 2001 Nov 21;286(19):2400-1; author reply 2401-2. PMID: 11712929; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712928; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712927; CIN: JAMA. 2001 May 16;285(19):2508-9. PMID: 11368705; CIN: JAMA. 2003 Apr 16;289(15):1928; author reply 1929. PMID: 12697793; CIN: JAMA. 2001 Aug 1;286(5):533-5. PMID: 11476650; CIN: JAMA. 2001 Nov 21;286(19):2401-2. PMID: 11712931; ppublish
This study examined the degree to which humans compensate for a reduction in dietary fat by increasing energy intake. Thirteen females were randomly assigned to either a low-fat diet (20-25% of calories as fat) or a control diet (35-40% fat) for 11 wk. After a 7-wk washout period, the conditions were reversed for another 11 wk. Energy intake on the low-fat diet gradually increased by 0.092 kJ/wk resulting in a total caloric compensation of 35% by the end of the 11-wk treatment period. This failure to compensate calorically on the low-fat diet resulted in a deficit of 1.22 kJ/d and a weight loss of 2.5 kg in 11 wk, twice the amount of weight lost on the control diet. These results demonstrate that body weight can be lost merely by reducing the fat content of the diet without the need to voluntarily restrict food intake.
Life-style modification has been recommended by the National Cholesterol Education Program as the first approach to reduce serum lipid values and the risk for coronary heart disease. Presented are data from 4587 adults who attended a 3-week residential, life-style modification program consisting of a high-complex-carbohydrate, high-fiber, low-fat, and low-cholesterol diet combined with daily aerobic exercise, primarily walking. Total cholesterol values were reduced by 23%, from 6.06 to 4.66 mmol/L (234 to 180 mg/dL). Low-density cholesterol (LDL-C) values were also reduced by 23%, from 3.9 to 3.0 mmol/L (151 to 116 mg/dL), with most of the change occurring during the first 2 weeks. Male subjects showed a greater reduction in total cholesterol (24.4% vs 20.8%) and LDL-C (25% vs 19.4%) values compared with female subjects. Follow-up studies for 18 months on a small group showed that, in most cases, continued compliance with the program maintained total cholesterol values well below 5.18 mmol/L (200 mg/dL), the level recommended by the National Cholesterol Education Program. High-density cholesterol (HDL-C) was reduced by 16%, but the ratio of total cholesterol to HDL-C was reduced by 11%. Female subjects showed a greater drop in HDL-C values than did male subjects (19.4% vs 11.6%). Serum triglyceride values were reduced by 33%, from 2.29 to 1.54 mmol/L (200 to 135 mg/dL); again, male subjects showed a greater reduction than the did female subjects (37.9% vs 22.5%). Body weight was also significantly reduced, 5.5% for male subjects and 4.4% for female subjects. These results show that most adults can significantly reduce serum lipid values and the risk for atherosclerosis and its clinical sequelae through life-style modification consisting of diet and exercise.
The first report from the Framingham Study that demonstrated an inverse relationship between high-density lipoprotein cholesterol (HDL-C) and the incidence of coronary heart disease (CHD) was based on four years of surveillance. These participants, aged 49 to 82 years, have now been followed up for 12 years, and this report shows that the relationship between the fasting HDL-C level and subsequent incidence of CHD does not diminish appreciably with time. Since a second measurement of HDL-C is available eight years after the initial determination, the relationship of HDL-C measurements on the same subjects at two points in time is examined. This second HDL-C measurement is also used in a multivariate model that includes cigarette smoking, relative weight, alcohol consumption, casual blood glucose, total cholesterol, and blood pressure. It is concluded that even after these adjustments, nonfasting HDL-C and total cholesterol levels are related to development of CHD in both men and women aged 49 years and older. Study participants at the 80th percentile of HDL-C were found to have half the risk of CHD developing when compared with subjects at the 20th percentile of HDL-C.
A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
Cardiovascular conditioning reduces resting myocardial oxygen demand by lowering systolic blood pressure and heart rate. Lower myocardial oxygen demand at rest would be expected to be associated with a decrease in resting myocardial blood flow and, consequently, an increase in myocardial flow reserve as the ratio of hyperemic to resting blood flow. However, the effect of controlled exercise together with a low-lipid diet on myocardial blood flow and flow reserve has not been examined in humans.
Myocardial blood flow at rest and after dipyridamole-induced hyperemia (0.56 mg/kg i.v.) was quantified with [13N]ammonia and positron emission tomography in 13 volunteers before and upon completion of a 6-week program of cardiovascular conditioning and a low-fat diet. Exercise capacity and serum lipid profiles were also assessed at the start and finish of the program. Eight normal volunteers of similar age not participating in the conditioning program served as a control group. Cardiovascular conditioning lowered the resting rate-pressure product (8859 +/- 2128 versus 7450 +/- 1496, P < .001), serum cholesterol (217 +/- 36 versus 181 +/- 26 mg/dL), LDL cholesterol (140 +/- 32 versus 114 +/- 24 mg/dL), and triglycerides (145 +/- 53 versus 116 +/- 33 mg/dL, all P < .05). Exercise tolerance (metabolic equivalent of the task, METs) improved significantly from 10.0 +/- 3.0 to 14.4 +/- 3.6 (P < .01). Resting blood flow decreased (0.78 +/- 0.18 versus 0.69 +/- 0.14 mL.g-1.min-1, P < .05), whereas hyperemic blood flow increased (2.06 +/- 0.35 versus 2.25 +/- 0.40 mL.g-1.min-1, P < .05), resulting in an improved myocardial flow reserve (2.82 +/- 1.07 versus 3.39 +/- 0.91, P < .05). Overall, the myocardial flow reserve was significantly related to exercise performance (METs). In the control group, no changes in resting rate-pressure product, serum cholesterol levels, exercise performance, resting or hyperemic myocardial blood flow, or flow reserve were observed.
Short-term cardiovascular conditioning together with a low-fat diet results in an improved myocardial flow reserve by lowering resting blood flow and increasing coronary vasodilatory capacity. These changes are associated with an improved exercise capacity and may offer a protective effect in patients with coronary artery disease.
The clinical events resulting from atherosclerosis are directly related to the oxidation of lipids in LDLs that become trapped in the extracellular matrix of the subendothelial space. These oxidized lipids activate an NF kappa B-like transcription factor and induce the expression of genes containing NF kappa B binding sites. The protein products of these genes initiate an inflammatory response that initially leads to the development of the fatty streak. The progression of the lesion is associated with the activation of genes that induce arterial calcification, which changes the mechanical characteristics of the artery wall and predisposes to plaque rupture at sites of monocytic infiltration. Plaque rupture exposes the flowing blood to tissue factor in the lesion, and this induces thrombosis, which is the proximate cause of the clinical event. There appear to be potent genetically determined systems for preventing lipid oxidation, inactivating biologically important oxidized lipids, and/or modulating the inflammatory response to oxidized lipids that may explain the differing susceptibility of individuals and populations to the development of atherosclerosis. Enzymes associated with HDL may play an important role in protecting against lipid oxidation in the artery wall and may account in part for the inverse relation between HDL and risk for atherosclerotic clinical events.
Study subjects (6 women and 5 men) over the age of 40 years with fasting low-density lipoprotein cholesterol concentrations > 130 mg/dL were studied during three 5-week diet phases and one 10-week phase: baseline (36% fat: 13% saturated fatty acids [SFA], 12% monounsaturated fatty acids [MUFA], 8% polyunsaturated fatty acids [PUFA], and 128 mg cholesterol/1000 kcal); reduced fat (29% fat: 7% SFA, 9% MUFA, 11% PUFA, and 85 mg cholesterol/1000 kcal); and two low fat (15% fat: 5% SFA, 5% MUFA, 3% PUFA, and 73 mg cholesterol/1000 kcal). Body weight was maintained during the first three 5-week phases (baseline, reduced fat, and low fat [-->energy]) and decreased during the last 10-week phase when the low-fat diet was provided such that the subjects determined, in part, their caloric intake (low fat [decreases energy]). Mean body weight declined by 0.62 +/- 0.47 kg/wk during the first 5 weeks and 0.43 +/- 0.43 kg/wk during the second 5 weeks of the 10-week low-fat (decreases energy) period. Relative to the baseline diet, plasma cholesterol concentrations decreased from 226 +/- 33 to 195 +/- 19 (-13%), 208 +/- 22 (-7%), and 190 +/- 19 (-15%) mg/dL when the subjects consumed the reduced-fat, low-fat (--> energy), and low-fat (decreases energy) diets, respectively. Low-density lipoprotein cholesterol concentrations decreased from 158 +/- 28 to 128 +/- 16 (-18%), 134 +/- 17 (-14%), and 119 +/- 15 (-23%) mg/dL when the subjects consumed the reduced-fat, low-fat (--> energy), and low-fat (decreases energy) diets, respectively. High-density lipoprotein cholesterol concentrations decreased from 48 +/- 11 to 42 +/- 9 (-10%), 35 +/- 7 (-25%), and 38 +/- 8 (-18%) mg/dL when the subjects consumed the reduced-fat, low-fat (--> energy), and low-fat (decreases energy) diets, respectively. Triglyceride concentrations increased from 110 +/- 32 to 115 +/- 31 (8%), 188 +/- 76 (75%), and 130 +/- 32 (22%) mg/dL when the subjects consumed the reduced-fat, low-fat (--> energy), and low-fat (decreases energy) diets, respectively. Maximal changes in plasma lipid concentrations were observed after the first 5 weeks of the low-fat (decreases energy) diet phase despite continued weight loss throughout the entire 10-week diet period.(ABSTRACT TRUNCATED AT 400 WORDS)
Epidemiologic studies have correlated fasting and postload insulin levels with the risk of coronary heart disease, assuming that insulin levels are reliable markers of insulin resistance. However, this assumption has not been systematically studied. The author measured insulin response to an oral glucose load and quantitated insulin resistance using the euglycemic hyperinsulinemic clamp technique to evaluate the correlation between insulin level and the degree of insulin resistance in individuals with varying degrees of glucose tolerance. Subjects were randomly selected from previous population studies done in 1987-1989 at the Department of Medicine of the University of Kuopio in east Finland. Altogether, 50 subjects with normal glucose tolerance, 28 with impaired glucose tolerance, and 54 with non-insulin-dependent diabetes mellitus were studied. Correlations of insulin resistance (whole-body glucose uptake in clamp studies) with fasting or postload insulin levels were remarkably consistent, ranging from -0.58 to -0.74 (p < 0.01) in subjects with normoglycemia. In contrast, corresponding correlations were substantially weaker in subjects with impaired glucose tolerance and non-insulin-dependent diabetes. Among these subjects, only the fasting insulin level correlated significantly with insulin resistance (-0.47, p < 0.05 and -0.48, p < 0.01, respectively). The authors conclude that in population studies, only the fasting insulin level should be used as a marker of insulin resistance, particularly in subjects with abnormal glucose tolerance.
2',7'-Dichlorofluorescein and dihydrorhodamine 123 were evaluated as probes for detecting changes in intracellular H2O2 in cultured endothelial cells. Stable intracellular levels of these probes were established within 15 min of exposure to the probe in culture medium. With continued presence of the probe in the medium, intracellular levels were unchanged for 1 h. However, if medium without the probes was used after intracellular loading had occurred, there was a greater than 90% loss of intracellular dichlorofluorescin, dichlorofluorescein, and dihydrorhodamine 123 while intracellular rhodamine 123 decreased by only 15%. Exposure of endothelial cells to exogenous 100 microM H2O2 for 1 h increased intracellular rhodamine 123 by 83%, but there was a reproducible decrease of 53% in intracellular dichlorofluorescein. Exposure to 0.05 mM BCNU plus 10 mM aminotriazole for 2 h increased intracellular rhodamine 123 by 111%. In vitro studies of dihydrorhodamine 123 oxidation were similar to previous reports of dichlorofluorescin oxidation. Oxidation of dihydrorhodamine 123 does not occur with H2O2 alone, but is mediated by a variety of secondary H2O2-dependent intracellular reactions including H2O2-cytochrome c and H2O2-Fe2+. Our results suggest that detection of increased oxidation of these probes in endothelial cells is most useful as a marker of a change in general cellular oxidant production.
Activation of the microvasculature is a major component of the inflammatory response. During inflammation the vascular endothelium not only becomes more permeable to plasma proteins but also develops adhesion molecules that initiate the local immigration of leukocytes. We describe herein the in vivo changes in the three major vascular adhesion molecules during the development and healing of two types of rabbit dermal inflammatory lesions: (1) acute lesions produced in rabbits by the topical application of 1% sulfur mustard (SM, the military irritant/toxicant); and (2) chronic (immune-mediated) lesions produced in rabbits by intradermal injections of Mycobacterium bovis (BCG), the vaccine strain of tubercle bacillus. In each case, frozen tissue sections were made from lesions of various ages and stained immunohistochemically for von Willebrand (vW) factor to measure the total functional microvasculature. The sections were also stained immunohistochemically for the vascular endothelial adhesion molecules ICAM-1, ELAM-1 (E-selectin), and VCAM-1, and for the leukocyte ligands for ICAM-1: LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18). Infiltrating monocytes and lymphocytes expressed the LFA-1 ligand and infiltrating PMN expressed the MAC-1 ligand. The area of stained microvasculature per square millimeter of tissue section was determined with the use of a computerized image analyzer. Edema and cell infiltration spread apart the microvessels, changing the number of microvessels per square millimeter of tissue section. Three methods of assessing such changes are presented. In SM lesions, endothelial ICAM levels were decreased from normal by about 50% at 1 and 2 days (when the lesions reached their peak size) and returned to normal at 3 and 6 days (during the healing process). ELAM rose in peak SM lesions and remained high during healing. VCAM levels, however, were only elevated in the 6-day (almost healed) lesions. In BCG lesions the levels of endothelial ICAM and VCAM (and to a lesser extent ELAM) were increased at 9 days and remained so as the size of the lesions peaked at 23 days. During the healing phase at 37 days, the elevated ICAM and VCAM levels decreased but the slightly increased ELAM levels persisted. These findings indicate that ELAM plays a major role in acute inflammation and that VCAM and ICAM play major roles in chronic inflammation. VCAM is known to be monocyte and lymphocyte selective.
Oxidants such as reactive oxygen species (ROS) have been shown to participate in myocardial ischemia/reperfusion injury. While many studies report a burst of ROS at reperfusion, few reports have presented evidence of significant ROS generation during ischemia. Our previous studies of cultured cardiomyocytes indicated that antioxidants are most effective when given prior to reperfusion during ischemia. Therefore, we hypothesized that significant ROS generation may occur during ischemia prior to reperfusion. We tested this in a perfused isolated cardiomyocyte system (i.e. without neutrophils, endothelial cells, or xanthine/xanthine oxidase) during simulated ischemia/reperfusion while measuring oxidant generation using intracellular fluorescent probes. During ischemia, the ROS probes dihydroethidium and 2',7'-dichlorofluorescin were significantly oxidized, suggesting superoxide and H2O2 generation. At reperfusion following 1 h ischemia, these probes suggested a further burst of H2O2 and hydroxyl radicals. The antioxidants 2-mercaptopropionyl glycine and 1,10-phenanthroline used during ischemia attenuated oxidant generation, increased cell viability, and improved return of contraction after ischemia. To further evaluate the relationship between residual O2 and ROS generation, we administered O2 scavengers during ischemia and measured corresponding changes in oxidant generation, cell viability and contraction during reperfusion. Enzymatic scavenging of residual O2 during ischemia (reducing PO2 from 3.5 to 2.5 tau) paradoxically improved subsequent viability and contraction. These results indicate that cultured cardiomyocytes generate significant ROS during ischemia. This ROS generation is related to residual O2 present during ischemia and contributes significantly to the cellular injury seen at reperfusion.